Ten-Year Results Following One-Stage Septic Hip Exchange in the Management of Periprosthetic Joint Infection.

BACKGROUND: Although 2-stage revision is still considered the gold standard for surgical management of periprosthetic joint infection (PJI), 1-stage revision has been reported to be as effective. Long-term reports for 1-stage revision in hip PJIs are lacking. METHODS: We reviewed our 10-11 years of results of 85 patients who underwent 1-stage exchange of the hip with an antibiotic-loaded bone cemented prosthesis due to PJI to determine the following: (1) What is the infection-free survival? (2) What is the overall survival? and (3) What are the long-term clinical outcomes? All 1-stage revision total hip arthroplasties (THAs) for infection between January 2006 and December 2007, with a minimum 10-year follow-up (range 10-11), were included in this retrospective cohort. Patients from another country or patients who were unable to participate were excluded. Eighty-five patients with a hip PJI were available at the last follow-up. Thirty-seven patients died during the 10-year study. Harris Hip Scores were recorded before the surgery and at last follow-up. Failures are reported as infection-related or aseptic. RESULTS: The 10-year infection-free survival was 94% and the surgery-free survival was 75.9%. The Harris Hip Scores improved from 43 (range 3-91) to 75 (range 10-91) (P < .001). The main indication for re-revision after 1-stage exchange was instability (10/20 patients). CONCLUSION: One-stage exchange of the hip for PJI is a reliable treatment option with high rate of infection control and long-lasting favorable outcomes.

High bacterial contamination rate of electrocautery tips during total hip and knee arthroplasty.

PURPOSE: The aim of the study was to quantify the bacterial contamination rate of electrocautery tips during primary total joint replacement (TJR), as well as during aseptic and septic revision TJR. METHODS: A total of 150 electrocautery tips were collected between April and July 2017. TJR surgeries were divided into three groups: (1) primary, (2) aseptic and (3) septic revisions. In each group, a total of 50 electrocautery tips were collected. A monopolar electrocautery with a reusable stainless-steel blade tip was used in all cases. The rate of bacterial contamination was determined for all groups. Correlation of exposure time and type of surgery was analyzed. RESULTS: The overall bacterial contamination rate was 14.7% (95% CI 9.4 to 21.4%). The highest contamination rate occurred in the septic revision group (30.0%; 95% CI 17.9 to 44.6%), followed by the primary cases group (10.0%; 95% CI 3.3 to 21.8%) and the aseptic revision group (4.0%; 95% CI 0.5 to 13.7%). Exposure time did not affect the bacterial contamination rate. In 12 out of 15 (80%) contaminations identified in the septic group, we found the same causative microorganism of the prosthetic joint infection on the electrocautery tip. CONCLUSIONS: The bacterial contamination of the electrocautery tips is relatively high, especially during septic hip revision arthroplasty. Electrocautery tips should be changed after debridement of infected tissue.

Complication rates after total ankle arthroplasty in one hundred consecutive prostheses.

INTRODUCTION: Total ankle arthroplasty is increasingly used as an alternative to arthrodesis to treat advanced ankle arthritis. However, the outcomes and postoperative complications are poorly described. PATIENTS AND METHODS: Between March 2005 and May 2010 114 S.T.A.R. prostheses were implanted by one surgeon at our institution. We retrospectively analysed the demographics, clinical outcomes and radiographic characteristics of 100 ankle prostheses (97 patients). RESULTS: The average follow up was 36 months. The average preoperative AOFAS score of 36.87 (22-58) significantly increased to 75.99 postoperative. A total of 87 % of the patients reported a better life quality. Twenty-seven ankles incurred complications after primary surgery, and 21 prostheses required revision surgery, including four patients who required arthrodesis. CONCLUSION: Our study shows a high satisfaction rate after total ankle replacement and clear pain relief. Patients with a body mass Index higher than 30 showed a higher rate of complications. Compared with ankle fusion, the rates of complications are comparable.

Failed joint unloading implant system in the treatment of medial knee osteoarthritis.

In the setting of end-stage osteoarthritis of the knee, total knee arthroplasty is the gold-standard treatment. Recently, a minimally invasive, joint preserving treatment option in the treatment of medial osteoarthritis of the knee has been developed. It is called the KineSpring(®) (Moximed(®) International GmbH, Zurich, Switzerland). The goal of this novel device is to reduce medial compartment loading without significantly affecting the loading of the lateral compartment. In this context, the current authors present a case of device failure using these new implants, which at 7 months post-op necessitated revision surgery with complete removal of the device.

10-year results following impaction bone grafting of major bone defects in 29 rotational and hinged knee revision arthroplasties: a follow-up of a previous report.

BACKGROUND AND PURPOSE: Substantial bone loss in revision total knee arthroplasty (TKA) is a challenging problem. We studied whether impaction bone grafting provides long-term restoration of bone stock in the treatment of major bone defects in revision surgery of rotational and hinged knee arthroplasties (LINK Endo-Model). PATIENTS AND METHODS: Between 1996 and 2006, 29 knees in 29 patients underwent revision procedures of rotational and hinged knee arthroplasties using impaction bone grafting (IBG) to reconstruct major bone defects. At the latest follow-up, the clinical examination included the Knee Society score (KSS), standardized radiographs, and a questionnaire for the WOMAC score. RESULTS: After a mean follow-up of 10 (6-13) years, 14 knees with 19 IBG reconstructions (5 total, 9 partial revisions) had failed. 12 knees were treated with re-revision surgery mean 5 (1-12) years after the first revision, due to mechanical failure and aseptic loosening of the components. In all these failed cases, the surgeon observed a lack of incorporation with bone graft resorption in the femur or tibia during the re-revision procedure. In all 15 knees that were not re-revised, with 21 reconstructions (6 total, 9 partial revisions), an improvement in the combined KSS score (knee score + function score) of 60 points (p < 0.001) was found at the latest follow-up. In 12 of these knees, a clear incorporation with no visible radiolucent lines around the component and no sign of substantial graft resorption was noted, while unclear radiographic graft incorporation was seen in 3 knees. INTERPRETATION: Our results clearly indicate that IBG alone is not a methodologically sound technique in the revision of rotational and hinged knee arthroplasties.

Histological ex vivo analysis of retrieved human tantalum augmentations.

PURPOSE: The characteristics of tantalum augment osseointegration in human ex vivo specimens from re-revision procedures are unknown and limited data in this regard is available. The purpose of this study was to investigate the osseointegration pattern into porous tantalum augmentations harvested during re-revision procedures. METHODS: Between 2007 and 2010 a total of 324 hip and knee revisions with a tantalum augmentation were performed in our institution. Out of this cohort, seven patients (2.2 %) had to be re-revised. To analyse the status of trabecular ingrowth in the retrieved cases (four hips, three knees), all specimens were analysed by contact radiography, subjected to undecalcified processing, histology, thin-section analysis and backscattered electron imaging. RESULTS: Trabecular and vascular ingrowth could be found along the bone-augment-interface in two of seven revised specimens, respectively. The depth of bone ingrowth reached up to 2.6 mm. However, the analysis of the remaining cases revealed no bony ingrowth into trabecular metal. Rather, large parts of the implants were embedded in cement or pores were filled with autologous bone. CONCLUSIONS: Although the cause for the missing bony ingrowth seems to be multifactorial, some fundamental conditions, such as the provision of the greatest possible interface between the tantalum implant and the host bone, should be met and thus, bone cement and autologous bone grafts should be used with caution.

Effects of increased bone formation on fracture healing in mice.

BACKGROUND: Fracture healing is a complex and sequential process. One important step in fracture healing is callus remodeling. As we could previously show, an increase of osteoclast bone resorption as a result of estrogen deficiency impairs the fracture healing process. Therefore, the aim of our study was to analyze whether an increased bone formation, as the counterpart of bone resorption in callus remodeling, would accelerate the fracture healing process. METHODS: Standardized femoral fractures were produced in 10-week-old control, leptin-deficient (ob/ob), and leptin receptor-deficient (db/db) mice using a guillotine-like fracture device. Accordingly, the fractures were intramedullary stabilized. The ob/ob and db/db mice are known to have a twofold increase in bone formation in comparison with normal wildtype mice. At different stages of fracture healing, contact X-ray, histologic, and biomechanical analyses were performed. RESULTS: We observed that a twofold increase in bone formation leads to an accelerated periosteal callus formation followed by callus remodeling. As compared with the control group, chondrocytes area was increased, and the subsequent mineralization appeared earlier. In the late stage of fracture healing, the ob/ob and db/db mice showed a thinner but increased mineralized cortex. Biomechanical testing confirmed the beneficial effects of an increased bone formation on restoration of biomechanical competence. CONCLUSION: These results indicate that bone formation is of major importance in all stages of fracture healing. A twofold increase in bone formation is able to significantly accelerate the fracture healing process of long bones at least in mice. Therefore, an increase in bone formation would be a possible pharmaceutical target to enhance fracture healing.

The distal radius, the most frequent fracture localization in humans: a histomorphometric analysis of the microarchitecture of 60 human distal radii and its changes in aging.

BACKGROUND: The distal radius is the most frequent fracture localization in humans. Although younger patients receive a distal radius fracture after an adequate trauma, elderly patients suffer fractures through low-energy mechanisms. Low-energy fractures are hallmarks of osteoporosis. Osteoporotic changes of the distal radius are well described by DXA and peripheral quantitative computed tomography measurements. However, to date, the effects of aging on the microarchitecture of the distal radius have not been investigated. METHODS: To investigate whether the microarchitecture of the human distal radius shows osteoporotic changes in bone mass and structure during aging, we dissected out 60 complete human distal radii from 30 age- and gender-matched patients at autopsy. Each of the three different age groups (group I: 20-40 years, group II: 41-60 years, group III: 61-80 years) was represented by 10 autopsy cases and 20 specimens (double-sided extraction), respectively. The specimens were analyzed by peripheral quantitative computed tomography, contact-radiography, and histomorphometry. RESULTS: We observed a significant age-related decrease in bone mass, bone mineral density and an increase in typical osteoporotic changes of the bone microarchitecture in female distal radius specimens. Comparable observations of age-related changes have not been made in male specimens. CONCLUSIONS: The distal radius is a location of osteoporosis-specific bone changes. Our data provide evidence for the occurrence of typical osteoporotic changes, especially postmenopausal osteoporotic changes, in the distal radius during aging.

Mid-term results of 155 patients treated with a collum femoris preserving (CFP) short stem prosthesis.

Short stem prostheses that preserve the femoral neck are becoming more and more popular. The CFP (collum femoris preserving) has been introduced especially for the treatment of younger patients. However, information about remodelling, complications and learning curve are thus far rare. We present a retrospective study of 155 patients (average age 59.3 ± 9.9 years) who underwent total hip replacement with the CFP prosthesis. Follow-up was obtained 74.3 ± 9.4 months postoperatively. The Harris hip score revealed excellent and good results in 96%. One stem had to be exchanged due to aseptic loosening revealing a survival rate of 99% and 100% for stem and cup, respectively. Radiological analysis showed typical patterns of remodelling with appearance of cortical thickening predominantly in the distal part of the prosthesis. Implant related revision rate was <1%, with further complication rate independent of the surgeon's individual experience. With regard to outcome, survivorship and complication rate, the medium-term results of the CFP prosthesis are promising.

Variability in stem taper surface topography affects the degree of corrosion and fretting in total hip arthroplasty.

Degradation at the modular head-neck interface in total hip arthroplasty (THA) is predominately expressed in the form of corrosion and fretting, potentially causing peri-prosthetic failure by adverse reactions to metal debris. This retrieval study aimed to quantify variations in stem taper surface topographies and to assess the influence on the formation of corrosion and/or fretting in titanium alloy stem tapers combined with metal and ceramic heads. Four hip stem designs (Alloclassic, CLS, Bicontact and SL-Plus) were characterized using high-resolution 3D microscopy, and corrosion and fretting were rated using the Goldberg scoring scheme. Quantification of the taper surface topographies revealed a high variability in surface characteristics between threaded stem tapers: Alloclassic and CLS tapers feature deeply threaded trapezoid-shaped profiles with thread heights over 65 µm. The sawtooth-shaped Bicontact and triangular SL-Plus taper are characterized by low thread heights below 14 µm. Significantly lower corrosion and fretting scores were observed in lightly threaded compared to deeply threaded tapers in ceramic head combinations. No significant differences in corrosion or fretting scores with thread height were found in pairings with metal heads. Understanding the relationship between stem taper surface topography and the formation of corrosion and fretting could help to improve the performance of modern THAs and lead to longer-lasting clinical results.

Microarchitecture of the radial head and its changes in aging.

Fractures of the radial head are common; however, it remains to be determined whether the radial head has to be considered as a typical location for fractures associated with osteoporosis. To investigate whether the human radial head shows structural changes during aging, we analyzed 30 left and 30 right human radial heads taken from 30 individuals. The specimens taken from the left side were analyzed by peripheral quantitative computed tomography (pQCT) and micro-CT. The specimens taken from the right elbow joint were analyzed by radiography and histomorphometry. In these specimens pQCT revealed a significant decrease of total and cortical bone mineral density (BMD(to) BMD(co)) with aging, regardless of sex. Histomorphometry revealed a significant reduction of cortical thickness (Ct.Th), bone volume per tissue volume (BV/TV), and trabecular thickness (Tb.Th) in male and female specimens. In this context, mean BV/TV and mean trabecular number (Tb.N) values were significantly lower and, accordingly, mean trabecular separation (Tb.Sp) was significantly higher in female samples. The presented study demonstrates that the radial head is a skeletal site where different age- and sex-related changes of the bone structure become manifest. These microarchitectural changes might contribute to the pathogenesis of radial head fractures, especially in aged female patients where trabecular parameters (BMD(tr) and Tb.Sp) change significantly for the worse compared to male patients.

Effects of estrogen on fracture healing in mice.

BACKGROUND: Fracture healing is a complex and sequential process. One important step in fracture healing is callus remodeling. Estrogen deficiency is known to increase osteoclast bone resorption, whereas estrogen replacement can reverse this effect. Therefore, the aim of our study was to analyze whether estrogen deficiency and estrogen treatment, respectively, would affect callus remodeling in the fracture healing process. METHODS: Standardized femoral fractures were produced in 10 weeks old C57BL/6 mice using a guillotine-like fracture device. Mice were separated into three groups. The first group obtained a continuous administration of estrogen. Ovariectomy (OVX) was performed in the second group to generate an estrogen-deficiency model. The control group obtained no special treatment. At different stages of fracture healing, contact X-ray, micro-computed tomography, histologic, and biomechanical analyses were performed. RESULTS: We observed that, in early stages of fracture healing, OVX leads to an impaired periosteal callus formation. When compared with the control group, chondrocytes area was decreased, and the subsequent mineralization was less distinctive. In the late stage of fracture healing, the OVX mice showed a thin and porous cortex. In sharp contrast, estrogen treatment led to an enhanced fracture healing. Chondrocyte areas were larger, callus mineralization was increased, and the neocortex was thicker. Biomechanical testing confirmed the beneficial effects of estrogen on restoration of biomechanical competence. CONCLUSION: These results indicate that estrogen seems to be an important factor in all stages of fracture healing. The application of estrogens enhances fracture healing of long bones at least in mice.

Evaluation of anatomic landmarks and safe zones for screw placement in the atlas via the posterior arch.

Several studies have evaluated quantitative anatomic data for direct lateral mass screw fixation. To analyze anatomic landmarks and safe zones for optimal screw placement through the posterior arc of the human atlas, morphometric parameters of 41 adult native human atlas specimens were quantitatively measured. Internal dimensions of the atlas (lateral mass, maximum and minimum intraosseous screw length), minimum height and width of the posterior arc and optimal screw insertion angles were defined on pQCT scans. By this, an optimal posterior screw insertion point (OIP) and a preferable screw direction (PSD) through the posterior arch into the lateral mass of C1 were defined. External dimensions (transverse and sagittal diameter) as well as the width of the mid-portion of C1 lateral mass were significantly higher in male specimens. The mean height of the posterior arch at the vertebral artery groove was 4.1 +/- 0.8 mm in female and 4.6 +/- 0.9 mm in male specimens. The optimal screw insertion point was located 21.6 +/- 1.7 mm in female and 23.6 +/- 2.3 mm in male lateral from the posterior tubercle of C1 (P < 0.01). The preferable screw direction was a mean medial inclination of 7.9 +/- 1.9 degrees in female and 7.3 +/- 2.7 degrees in male specimens and a mean rostral direction of 2.4 +/- 1.8 degrees in female and 3.1 +/- 1.7 degrees in male specimens. In conclusion, the presented study provides information for the use and design of upper cervical spine instrumentation techniques, such as screw placement to C1 via the posterior arch. The characterization of working areas and safe zones (OIP, PSD) might contribute to a minimization of screw malposition in this highly demanding instrumentation technique.

Elevated HbA1c is not a risk factor for wound complications following total joint arthroplasty: a prospective study.

BACKGROUND: Controversies exist regarding the association of elevated serum glycated haemoglobin (HbA1c) levels and postoperative surgical site infection (SSI) or prosthetic joint infection (PJI) in the setting of total hip and knee arthroplasty (THA and TKA). The purpose of the current study was to determine the prevalence of unknown and uncontrolled diabetes mellitus (DM) in a consecutive series and to investigate the association between postoperative wound complications or SSI/PJI and elevated HbA1c in patients undergoing TJA. METHODS: In this prospective single-centre study, HbA1c was determined for patients undergoing elective primary, aseptic or septic revision THA and TKA, between September 2017 and March 2018. Prevalence of DM, unknown and uncontrolled diabetes were reported. Occurrence of 90-day wound healing disorders (WHD) as well as SSI or PJI were observed. Considering the HbA1c threshold ⩾6.5%, a comparative analysis between patients with and without WHD and SSI or PJI for the whole study cohort, as well as for each arthroplasty group, was performed. Receiver operating characteristic (ROC) curves were developed to quantify the predictive power of HbA1c with regard to WHD and infection complications. A total of 1488 patients were included for final analysis. There were 1127 primary THA and TKA (75.7%), 272 aseptic revisions (18.3%) and 89 septic revisions (6.0%). The known diabetic patients constituted 9.9% of the whole study cohort. RESULTS: The majority had uncontrolled DM (67%). Prevalence of unknown DM was 11.1%. The results reveal the prevalence for the German population and might be different in other regions. A total of 57 patients (3.7%) experienced postoperative wound or infectious complications. PJI occurred in only 5 patients (0.03%). There was no significant difference between patients with HbA1c <6.5% and patients with HbA1c ⩾6.5% (p = 0.092). CONCLUSIONS: We demonstrated that prevalence of unknown and uncontrolled DM in patients undergoing TJA is increasing, however; routine preoperative determination of the HbA1c value to prevent possible postoperative wound or infectious complications remains debatable. Larger studies investigating the optimal HbA1c level, as well as other predictors are required.

How reliable is the next generation of multiplex-PCR for diagnosing prosthetic joint infection compared to the MSIS criteria? Still missing the ideal test.

INTRODUCTION: Identification of the pathogen in case of a periprosthetic joint infection (PJI) remains 1 of the greatest challenges in septic surgery. Rapid germ identification enables timely, specific, antimicrobial therapy. The first multiplex PCR (polymerase chain reaction) generation (Unyvero-i60) enables germ detection within 5 hours with a sensitivity of 78.8% and a specificity of 100%. The aim of this study is to investigate the performance of the new generation of cartridges (Unyvero-ITI) of multiplex PCR in the case of a PJI. METHODS: In a prospective study, intraoperatively aspirated synovial fluid from 97 patients with aseptic or septic hip or knee revision surgery (49 aseptic, 48 septic) was examined with the multiplex PCR system (Unyvero-ITI) and the results were compared with the MSIS criteria. In addition, the time until the microbiological result was obtained in the event of a germ detection was documented. RESULTS: The multiplex PCR showed a germ detection with a sensitivity of 85.1% and a specificity of 98.0%. In 7 cases a false negative result was found and in one patient a false positive result was found. The general accuracy of this test procedure was 91.8%. The detection of germs was carried out within 5 hours with the multiplex PCR compared to 4.9 days in conventional microbiological diagnostics. CONCLUSIONS: The new generation of multiplex-PCR was able to improve germ detection. The possibility of prompt detection of germs offers the option of faster, targeted antimicrobial therapy. This diagnostic tool offers significant advantages, particularly in the context of an acute periprosthetic infection.

Anterior iliopsoas impingement due to a malpositioned acetabular component - effective relief by surgical cup reorientation.

BACKGROUND: Determining the aetiology of persistent pain following total hip arthroplasty (THA) can be challenging. Impingement of the iliopsoas muscle due to a malpositioned acetabular component after THA might be a potential cause of postoperative groin pain. METHODS: We retrospectively analysed the data of 12 consecutive patients from our orthopaedic department who underwent cup revision for painful iliopsoas impingement after primary THA. RESULTS: Thorough physical examination as well as radiological assessment of the included patients revealed that malpositioning of the acetabular component provoked iliopsoas impingement.The Harris Hip Score and the orientation of the acetabular component before and after surgical revision at an average follow-up of 56 months were analysed. CONCLUSIONS: We were able to demonstrate that surgical cup revision and reorientation resulted in distinctly improved scores and is a feasible option to effectively treat persistent iliopsoas impingement due to a malpositioned acetabular component following THA.

Are There Benefits In Early Diagnosis Of Prosthetic Joint Infection With Multiplex Polymerase Chain Reaction?

Purpose Identification of bacteria and susceptibility are fundamental in periprosthetic joint infection (PJI). Especially in the case of systemic inflammatory response syndrome (SIRS) rapid detection of pathogens is essential for proper therapy. Bacterial cultures are time consuming. The polymerase chain reaction (PCR) is a non-culture molecular method and is able to rapidly identify pathogens and their resistance genes. Multiplex PCR (mPCR) can amplify several different DNA sequences simultaneously. The aim of this study was to show the value of mPCR for early diagnosis of PJI. Methods 60 patients undergoing total hip or knee revisions were recruited in this prospective single-centre-study. Three groups were created: 26 patients with aseptic loosening (negative control), 26 patients with chronic PJI, and 8 patients with acute PJI/SIRS. We compared the results of joint aspirates obtained intraoperatively investigated by mPCR with the microbiology results of tissue specimens. Results The overall sensitivity of mPCR was 78.8% (95% CI, 61.1 - 91.0%), the specificity was 100% (95% CI, 87.2 - 100%), the negative predictive value was 79.4% (95% CI, 62.1 - 91.3%), the positive predictive value was 100% (95% CI, 86.8 - 100%), and the overall accuracy was 88.3% (95% CI, 77.4 - 95.2%). The overall accuracy in acute infections/SIRS (87.5%) was greater than in late chronic PJI (76.9%). In PJI the mPCR was able to provide the results within 5 hours whereas the mean time for cultures was 6.4 days. Conclusions Multiplex PCR is a reliable diagnostic tool in PJI management, especially in acute cases complicated with SIRS. Early diagnosis within several hours is possible, targeted antibiotic treatment can be started promptly.

Increased bone formation in mice lacking apolipoprotein E.

UNLABELLED: ApoE is a plasma protein that plays a major role in lipoprotein metabolism. Here we describe that ApoE expression is strongly induced on mineralization of primary osteoblast cultures. ApoE-deficient mice display an increased bone formation rate compared with wildtype controls, thereby showing that ApoE has a physiologic function in bone remodeling. INTRODUCTION: Apolipoprotein E (ApoE) is a protein component of lipoproteins and facilitates their clearance from the circulation. This is confirmed by the phenotype of ApoE-deficient mice that have high plasma cholesterol levels and spontaneously develop atherosclerotic lesions. The bone phenotype of these mice has not been analyzed to date, although an association between certain ApoE alleles and BMD has been reported. MATERIALS AND METHODS: Primary osteoblasts were isolated from newborn mouse calvariae and mineralized ex vivo. A genome-wide expression analysis was performed during the course of differentiation using the Affymetrix gene chip system. Bones from ApoE-deficient mice and wildtype controls were analyzed using radiography, micro CT imaging, and undecalcified histology. Cellular activities were assessed using dynamic histomorphometry and by measuring urinary collagen degradation products. Lipoprotein uptake assays were performed with (125)I-labeled triglyceride-rich lipoprotein-remnants (TRL-R) using primary osteoblasts from wildtype and ApoE-deficient mice. Serum concentrations of osteocalcin were determined by radioimmunoassay after hydroxyapatite chromatography. RESULTS: ApoE expression is strongly induced on mineralization of primary osteoblast cultures ex vivo. Mice lacking ApoE display a high bone mass phenotype that is caused by an increased bone formation rate, whereas bone resorption is not affected. This phenotype may be explained by a decreased uptake of triglyceride-rich lipoproteins by osteoblasts, resulting in elevated levels of undercarboxylated osteocalcin in the serum of ApoE-deficient mice. CONCLUSION: The specific induction of ApoE gene expression during osteoblast differentiation along with the increased bone formation rate observed in ApoE-deficient mice shows that ApoE has a physiologic role as a regulator of osteoblast function.