The zonal evolution of collagen-network morphology quantified in early osteoarthritic grades of human cartilage.

Objective: We aimed to directly quantify the zone-specific evolution in morphology of collagen fibers and networks in human cartilage during the progression of early osteoarthritis. Collagen fibers exhibit depth-dependent orientations and diameters crucial to their mechanical roles. Cartilage degenerates in osteoarthritis, affecting the morphology of the collagen network and ultimately the intra-tissue mechanics. Design: We obtained specimens of human cartilage from healthy human knees ( n = 3 ) and from total knee arthroplasties ( n = 5 ). We utilized TEM and custom image analyses to visualize and quantify distributions in principal orientation, dispersion (about the principal orientation), and diameter of collagen fibers in the early grades of OA within each through-thickness zone. We then used histological and statistical analyses to probe for significant changes in the zone-specific evolution in collagen-network morphology as a function of Osteoarthritis Research Society International (OARSI) grade. Results: Dispersion in the alignment of collagen fibers increased with progression of early OA in both the superficial and deep zones, and decreased in the middle zone, while principal orientation did not change significantly. The non-normal and right-skewed distributions in fiber diameters did not evolve with the progression of OA. Conclusions: We provide the research community with quantitative data (1) on the through-thickness morphology of collagen in healthy cartilage and (2) on the evolution of through-thickness morphology of collagen with progressing early OA. Such quantitative data facilitate an improved mechanistic understanding of the progression of OA, and may facilitate identifying image-based biomarkers and treatment targets, and ultimately finding clinical interventions for OA.

Reductions in Race and Ethnic Disparities in Hospital Readmissions Following Total Joint Arthroplasty from 2005 to 2015.

BACKGROUND: Racial and ethnic disparities in hospital readmissions following total joint arthroplasty present opportunities for reducing cost and improving health equity. Despite efforts to reduce readmissions following total joint arthroplasty in the general population, no studies have documented the impact of these efforts on racial and ethnic disparities in total joint arthroplasty readmissions. The purpose of this study was to determine whether comprehensive efforts to reduce hospital readmissions following total joint arthroplasty have impacted racial and ethnic disparities in readmission rates during the period from 2005 to 2015. METHODS: We conducted a retrospective analysis comparing patients readmitted and not readmitted to the hospital within 30 days of a total joint arthroplasty by estimating logistic regression models for clustered data using generalized estimating equations (GEEs) in R. Connecticut hospital discharge data for patients admitted for International Classification of Diseases, Ninth Revision (ICD-9) procedure codes 81.51 and 81.54 (Current Procedural Terminology [CPT] codes 27130 and 27447) during the 2005 to 2015 U.S. Centers for Medicare & Medicaid Services (CMS) fiscal years were analyzed. Models included quadratic terms to capture nonlinear time trends in readmissions, as well as terms for the statistical interaction between race or ethnicity and both the linear and quadratic time trends in predicting the odds of readmission. RESULTS: There were 102,510 total admissions to Connecticut hospitals for total joint arthroplasty from 2005 to 2015. The 30-day (all-cause) readmission rate declined from 5.1% in 2005 to 3.6% in 2015, with a steeper downward trend observed from 2009 to 2015. The results from logistic models indicated that black patients (odds ratio [OR], 1.68; p < 0.0001) and Hispanic patients (OR, 1.48; p < 0.0001) were significantly more likely to be readmitted within 30 days of discharge following a total joint arthroplasty than white patients over the study period. The significant interaction of black race and the quadratic time trend in models capturing nonlinear trends in readmission over time indicated that the readmission rates for black patients increased compared with those for white patients from 2005 through 2008 and decreased relative to those for white patients from 2009 to 2015 (OR, 0.24; p = 0.030). CONCLUSIONS: Data from Connecticut hospitals show that 30-day readmissions following a total joint arthroplasty declined by 1.5 percentage points from 2005 to 2015, and that this decline was much more pronounced among black patients, resulting in the narrowing of racial disparities in readmission following a surgical procedure. CLINICAL RELEVANCE: Racial and ethnic minorities have historically been at increased risk for complications and readmission following hospital-based surgical care. This analysis of readmission following total joint arthroplasty reveals that such disparities are remediable and should foster further research on the primary drivers of and remedies for readmission disparities.

Impact of Resilience on Outcomes of Total Knee Arthroplasty.

BACKGROUND: Resilience, defined as the ability to bounce back from stress, has been suggested as a predictor of surgical outcomes. The purpose of this study is to examine the relationship between resilience and patient-reported outcomes following primary elective total knee arthroplasty (TKA). We hypothesized that patients exhibiting greater preoperative resilience would report better outcome scores. METHODS: A prospective cohort of 153 patients (74 male, 79 female) undergoing primary elective TKA completed questionnaires preoperatively and at 3 and 12 months following their index procedure. The validated Brief Resilience Scale was used to evaluate resilience. Hierarchical multiple linear regression was used to analyze the effect of resilience on KOOS-JR (Knee Injury and Osteoarthritis Outcome Score JR) and PROMIS-10 (Patient-Reported Outcomes Measurement Information System) outcome scores. RESULTS: At 12 months, the change in the coefficient of determination (R2) attributable to preoperative resilience was 0.101 (P < .001) and 0.204 (P < .001) for physical and mental health, respectively. Although there was expected improvement in KOOS-JR scores following TKA, the effect of baseline resilience for this outcome was not significant. When evaluating resilience measured concurrently, there was significant correlation with both 3-month and 12-month KOOS-JR and PROMIS-10 outcome scores. CONCLUSION: Preoperative resilience is a significant predictor of overall physical and mental health outcomes at both 3 and 12 months. Greater concurrent resilience predicted better scores across all outcomes. These findings suggest that major elective surgery, like other traumatic events, can cause a change in resilience. Although functional improvements after TKA are expected, those patients who exhibit greater resilience at baseline are more likely to report an improved quality of life.

Do Patient Expectations Influence Patient-Reported Outcomes and Satisfaction in Total Hip Arthroplasty? A Prospective, Multicenter Study.

BACKGROUND: The relationship between patient expectations and patient-reported outcomes (PROs) in total hip arthroplasty (THA) patients is controversial. The purpose of this study was to examine the impact of preoperative patient expectations on postoperative PROs and patient satisfaction. METHODS: This was a prospective multicenter observational cohort study of primary THA patients. Preoperatively, patients completed Hospital for Special Surgery (HSS) Hip Replacement Expectations Survey (expectations), 12 item Short Form Survey (SF-12), University of California, Los Angeles (UCLA) activity score, and Hip Disability and Osteoarthritis Score (HOOS). Postoperatively at 6 months and 1 year, patients completed the Hospital for Special Surgery Hip Replacement Fulfillment of Expectations Survey (fulfillment of expectations), a satisfaction survey, and the same PROs as preoperatively. Stepwise multivariate regression models were created. RESULTS: A total of 207 patients were enrolled. Follow-up rate was 91% at 6 months and 92% at 1 year. Being employed and lower baseline HOOS predicted higher expectations (employment status: B = -7.5, P = .002; HOOS: B = -0.27, P = .002). Higher preoperative expectations predicted greater improvements in UCLA activity, SF-12 physical component score, and HOOS at 6 months (UCLA activity: B = 0.03, P = .001; SF-12 physical component score: B = 0.15, P = .001; HOOS: B = 0.20; P = .008) and UCLA activity at 1 year (B = 0.02, P = .004). Furthermore, higher expectations predicted higher postoperative satisfaction and fulfillment of expectations at 6 months (satisfaction: B = 0.21, P < .001; fulfillment of expectations: B = 0.30, P < .001) and higher fulfillment of expectations at 1 year (B = 0.17, P = .006). CONCLUSION: In patients undergoing THA, being employed and worse preoperative hip function predict of higher preoperative expectations of surgery. Higher expectations predict greater improvement in PROs, greater patient satisfaction, and the fulfillment of expectations. These findings can be used to guide patient counseling and shared decision making preoperatively.

Functional Gain and Pain Relief After Total Joint Replacement According to Obesity Status.

BACKGROUND: Obesity has been associated with lower function and more pain before and after total hip or knee replacement (THR or TKR). We examined the changes between preoperative and postoperative function and pain in a large representative U.S. cohort to determine if there was a relationship to obesity status. METHODS: Preoperative and 6-month postoperative data on function (Short Form-36 Physical Component Summary [PCS] score), joint pain (Hip disability and Osteoarthritis Outcome Score and Knee injury and Osteoarthritis Outcome Score), and body mass index (BMI) were collected from a national sample of 2,040 patients who had undergone THR and 2,964 who had undergone TKR from May 2011 to March 2013. Preoperative and postoperative function and pain were evaluated according to BMI status, defined as under or of normal weight, overweight, obese, severely obese, or morbidly obese. RESULTS: Patients undergoing THR were an average of 65 years of age; 59% were women, 94% were white, and 14% were severely or morbidly obese. A greater obesity level was associated with a lower (worse) PCS score at baseline and 6 months postoperatively. Severely and morbidly obese patients had less postoperative functional gain than the other BMI groups. A greater obesity level was associated with more pain at baseline but greater postoperative pain relief, so the average postoperative pain scores did not differ significantly according to BMI status. Patients undergoing TKR had an average age of 69 years; 61% were women, 93% were white, and 25% were severely or morbidly obese. A greater obesity level was associated with a lower PCS score at baseline and 6 months. The postoperative gain in PCS score did not differ by BMI level. A greater obesity level was associated with worse pain at baseline but greater pain relief at 6 months, so the average pain scores at 6 month were similar across the BMI levels. CONCLUSIONS: Six months after total joint replacement (TJR), severely or morbidly obese patients reported excellent pain relief and substantial functional gain that was similar to the findings in other patients. While obesity is associated with a greater risk of early complications, obesity in itself should not be a deterrent to undergoing TJR to relieve symptoms. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Higher Patient Expectations Predict Higher Patient-Reported Outcomes, But Not Satisfaction, in Total Knee Arthroplasty Patients: A Prospective Multicenter Study.

BACKGROUND: The relationship between patient expectations, patient-reported outcomes (PROs), and satisfaction in total knee arthroplasty (TKA) patients is not well understood. METHODS: We prospectively evaluated patients who underwent primary TKA at 4 institutions. Demographics were collected. Preoperatively, patients completed the Hospital for Special Surgery Knee Replacement Expectations Survey (HSS-KRES), SF-12, UCLA activity, and Knee Disability and Osteoarthritis Score. At 6 months and 1 year postoperatively, patients completed the Hospital for Special Surgery Knee Replacement Fulfillment of Expectations Survey (HSS-KRFES), a satisfaction survey, and PROs. Step-wise multivariate regression models were created. RESULTS: Eighty-three patients were enrolled. At 6 months and 1 year postoperatively, the follow-up rate was 84.3% and 92.7%, respectively. No demographics or preoperative PROs were predictive of HSS-KRES. Preoperative HSS-KRES did not predict postoperative satisfaction, but higher HSS-KRES predicted higher HSS-KRFES at 1 year, greater improvement in UCLA activity at 6 months and 1 year, and SF-12 Physical Composite Scale and Knee Disability and Osteoarthritis Score at 6 months. Higher HSS-KRFES predicted higher satisfaction at 6 months and 1 year. CONCLUSION: In TKA patients, preoperative expectations are not influenced by patient demographics or preoperative function. Higher preoperative expectations predict greater postoperative improvement in PROs and fulfillment of expectations. These findings highlight the importance of preoperative patient expectations on postoperative outcome.

Receipt of Pain Management Information Preoperatively Is Associated With Improved Functional Gain After Elective Total Joint Arthroplasty.

BACKGROUND: Poorly controlled postoperative pain may adversely affect total joint arthroplasty (TJA) patients' outcomes and associated healthcare cost. Understanding effective pain management after surgery is important to patients, surgeons, and hospitals. We evaluated patient-reported receipt of preoperative pain management information in a national prospective cohort evaluating postoperative pain and function following elective TJA. METHODS: Preoperative and 2-week and 6-month postoperative survey data of 1609 TJA patients collected between June 2013 and December 2014 were analyzed. Data included demographics, medical and musculoskeletal comorbidity, operative joint pain, physical function, and mental health. At 2 weeks postoperative, patients were asked if they had received pain management information prior to surgery, the content of that education, and pain management strategies. Descriptive statistics were performed. RESULTS: At 2 weeks post-TJA, one-third of patients reported not receiving information about pain management; an additional 11% did not find the information helpful. There were no differences preoperatively in demographics or clinical profiles between those who received pain information and those who did not. Patients who received pain information reported less pain 2 weeks postoperatively, greater use of non-narcotic pain care strategies, and better physical function scores at 6 months postoperatively. No differences in operative joint pain were identified at 6 months between education and noneducation groups. CONCLUSION: Forty-four percent of the patients reported that they did not receive/received unhelpful information regarding postoperative pain management, highlighting a need for improved patient education. In this sample, the lack of pain management information was associated with poorer 6-month postoperative function.

Safety and efficacy of continuous femoral nerve catheter with single shot sciatic nerve block vs epidural catheter anesthesia for same-day bilateral total knee arthroplasty.

In a retrospective analysis, we evaluated the safety and efficacy of peripheral nerve blocks (PNB) compared to epidural anesthesia in 221 consecutive patients undergoing same-day bilateral total knee arthroplasty (TKA). Primary outcome measures included: hypotension requiring physician intervention, number of blood transfusions, perioperative hespan and crystalloid consumption, incidences of respiratory desaturation, pruritis, urinary retention, and nausea/vomiting. The incidences of hypotension, urinary retention, and pruritis were all higher in the epidural group, compared to PNB. Epidural patients also required more blood transfusions and greater volumes of hespan and crystalloid. PNB are safe and efficacious modality of analgesia for same day bilateral TKA and provide adequate pain relief with a significant decrease in postoperative complications compared to epidural anesthesia.

Evaluation of the first-generation AAOS clinical guidelines on the prophylaxis of venous thromboembolic events in patients undergoing total joint arthroplasty: experience with 3289 patients from a single institution.

BACKGROUND: Patients undergoing total hip or total knee arthroplasty have risks that include venous thromboembolism. The American Academy of Orthopaedic Surgeons has promulgated guidelines for the preoperative assessment of patients with the primary objective of preventing pulmonary embolism. We aimed to evaluate and establish the utility of the first-generation American Academy of Orthopaedic Surgeons guidelines for the prophylaxis of venous thromboembolism in patients undergoing total joint arthroplasty at a single institution. METHODS: A prospective analysis of 3289 consecutive patients managed with total hip or total knee arthroplasty at the Connecticut Joint Replacement Institute between June 1, 2009, and April 30, 2011, was conducted. Data on age, sex, body mass index, American Society of Anesthesiologists classification, and a personal or family history of blood clots requiring long-term warfarin use were analyzed, as were data on a personal history of a malignant tumor, a bleeding disorder, gastrointestinal bleeding, or a hemorrhagic cerebrovascular accident. All patients were managed prophylactically with a specific algorithm based on the American Academy of Orthopaedic Surgeons guidelines. All of the patients were mobilized on postoperative day one, and pneumatic foot-pump compression was used for the duration of the hospitalization. RESULTS: Thirty-six major venous thromboembolic events were documented with Doppler ultrasound or computed tomography angiography, for a ninety-day incidence of 1.1% (95% confidence interval, 0.8% to 1.5%). A personal history of blood clots was significantly associated with a blood clot in the proximal part of the thigh or a pulmonary embolism, but a family history of blood clots and a personal history of a malignant tumor did not show a significant relationship with venous thromboembolism. The ninety-day incidence of venous thromboembolism was significantly different between total hip arthroplasty patients (0.56%; 95% confidence interval, 0.30% to 1.15%) and total knee arthroplasty patients (1.46%; 95% confidence interval, 1.01% to 2.10%). The risk was greater in high-risk total knee arthroplasty patients compared with high-risk total hip arthroplasty patients despite comparable prophylaxis with enoxaparin sodium for twenty-eight days. CONCLUSIONS: The prospective use of the first-generation American Academy of Orthopaedic Surgeons guidelines resulted in a low incidence of clinically important thromboembolic events in total hip and total knee arthroplasty patients. When properly used in these patients, the guidelines to minimize adverse outcomes are executable and effective. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Focused risk analysis: regression model based on 5,314 total hip and knee arthroplasty patients from a single institution.

We aimed to identify significant demographic, preoperative comorbidity and surgical predictors for major complications for use in the development of a risk prediction tool for a well-defined population as Total Joint Arthroplasty (TJA) patients. Data on 5314 consecutive patients who underwent primary total hip or knee arthroplasty from October 1, 2008 through September 30, 2011 at a single institution were used in a multivariate regression analysis. The overall incidence of a primary endpoint (reoperation during same admission, extended length of stay, and 30-day readmission) was 3.8%. Significant predictors include certain preexisting genitourinary, circulatory and respiratory conditions; ASA>2; advanced age and prolonged operating time. Mental health conditions demonstrate a strong predictive effect for subsequent serious complication(s) in TJA patients and should be included in a risk-adjustment tool.

Risk stratification algorithm for management of patients with metal-on-metal hip arthroplasty: consensus statement of the American Association of Hip and Knee Surgeons, the American Academy of Orthopaedic Surgeons, and the Hip Society.

There should be a low threshold to perform a systematic evaluation of patients with MoM hip arthroplasty as early recognition and diagnosis will facilitate the initiation of appropriate treatment prior to significant adverse biological reactions. A painful MoM hip arthroplasty has various intrinsic and extrinsic causes, and a systematic treatment approach based on the currently available data is presented to optimize management of MoM patients. The risk stratification algorithm presented will continue to develop as further evidence becomes available providing additional insights. While specialized tests such as metal ion analysis are useful modalities for assessing MoM hip arthroplasty, over-reliance on any single investigative tool in the clinical decision-making process should be avoided. Future research focusing on validation of the current diagnostic tools for detecting adverse local tissue reactions as well as optimization of MoM bearings and modular connections to further diminish wear and corrosion is warranted.

Local infiltration analgesia followed by continuous infusion of local anesthetic solution for total hip arthroplasty: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: We studied the efficacy of local infiltration analgesia in surgical wounds with 0.2% ropivacaine (50 mL), ketorolac (15 mg), and adrenaline (0.5 mg) compared with that of local infiltration analgesia combined with continuous infusion of 0.2% ropivacaine as a method of pain control after total hip arthroplasty. We hypothesized that as a component of multimodal analgesia, local infiltration analgesia followed by continuous infusion of ropivacaine would result in reduced postoperative opioid consumption and lower pain scores compared with infiltration alone, and that both of these techniques would be superior to placebo. METHODS: In this prospective, double-blind, placebo-controlled study, 105 patients were randomized into three groups: Group I, in which patients received infiltration with ropivacaine, ketorolac, and adrenaline followed by continuous infusion of 0.2% ropivacaine at 5 mL/hr; Group II, in which patients received infiltration with ropivacaine, ketorolac, and adrenaline followed by continuous infusion of saline solution at 5 mL/hr; and Group III, in which patients received infiltration with saline solution followed by continuous infusion of saline solution at 5 mL/hr.All patients received celecoxib, pregabalin, and acetaminophen perioperatively and patient-controlled analgesia; surgery was performed under general anesthesia. Before wound closure, the tissues and periarticular space were infiltrated with ropivacaine, ketorolac, and adrenaline or saline solution and a fenestrated catheter was placed. The catheter was attached to a pump prefilled with either 0.2% ropivacaine or saline solution set to infuse at 5 mL/hr.The primary outcome measure was postoperative opioid consumption and the secondary outcome measures were pain scores, adverse side effects, and patient satisfaction. RESULTS: There were no differences between groups in the administration of opioids in the operating room, in the recovery room, or on the surgical floor. The pain scores on recovery room admission and discharge and the floor were low and similar between groups. There were no differences in the incidence of adverse side effects among groups. Patient satisfaction with pain management was similar in all groups. CONCLUSIONS: Local infiltration analgesia alone or followed by continuous infusion of ropivacaine as part of multimodal analgesia provides no additional analgesic benefit or reduction in opioid consumption compared with placebo following total hip arthroplasty. LEVEL OF EVIDENCE: Therapeutic level I. See Instructions for Authors for a complete description of levels of evidence.

Cemented versus uncemented hemiarthroplasty for displaced femoral neck fractures: a prospective randomized trial with early follow-up.

OBJECTIVE: To prospectively compare the functional outcome associated with cemented and uncemented hemiarthroplasty. DESIGN: Prospective randomized control trial. SETTING: University-affiliated level 1 trauma center. PATIENTS/PARTICIPANTS: All individuals designated for hemiarthroplasty, older than 55 years, with a nonpathologic displaced femoral neck fracture and the ability to ambulate 10 feet independently before injury [269 patients (274 hips) presented with displaced femoral neck fracture, 130 patients (48.3%) enrolled, and 5 patients (3.8%) withdrew]. INTERVENTION: Hip hemiarthroplasty with a cemented femoral prosthesis (VerSys LD/Fx; Zimmer, Warsaw, IN) or an uncemented component (VerSys Beaded FullCoat; Zimmer, Warsaw, IN). MAIN OUTCOME MEASURES: Instrumental Activities of Daily Living and Physical Activities of Daily Living scales (Older Americans Resources and Services Instrument) and the Energy/Fatigue Scale. RESULTS: No statistically significant differences were present in the groups' preoperative or intraoperative characteristics, including American Society of Anesthesiologists grade, operative time, anesthesia time, use of perioperative ß-blockers, estimated blood loss, or the rate of intraoperative fracture. Postoperatively, no difference was found in hemoglobin level, transfusion rate, discharge disposition, or acute complication rate. At 30-day, 60-day, and 1-year follow-ups, no clinically or statistically significant differences were found in mortality, disposition, need for assistance with ambulation, Older Americans Resources and Services Activities of Daily Living subscales, or the Energy/Fatigue Scale. CONCLUSIONS: In the treatment of nonpathologic displaced femoral neck fractures, the use of cemented and uncemented femoral components is associated with similar functional outcome at 1 year. Practitioners may inform their clinical decisions using these equally good results. LEVEL OF EVIDENCE: Therapeutic Level II. See page 128 for a complete description of levels of evidence.

Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty.

This guideline supersedes a prior one from 2007 on a similar topic. The work group evaluated the available literature concerning various aspects of patient screening, risk factor assessment, and prophylactic treatment against venous thromboembolic disease (VTED), as well as the use of postoperative mobilization, neuraxial agents, and vena cava filters. The group recommended further assessment of patients who have had a previous venous thromboembolism but not for other potential risk factors. Patients should be assessed for known bleeding disorders, such as hemophilia, and for the presence of active liver disease. Patients who are not at elevated risk of VTED or for bleeding should receive pharmacologic prophylaxis and mechanical compressive devices for the prevention of VTED. The group did not recommend specific pharmacologic agents and/or mechanical devices. The work group recommends, by consensus opinion, early mobilization for patients following elective hip and knee arthroplasty. The use of neuraxial anesthesia can help limit blood loss but was not found to affect the occurrence of VTED. No clear evidence was established regarding whether inferior vena cava filters can prevent pulmonary embolism in patients who have a contraindication to chemoprophylaxis and/or known VTED.

The effects of patient age on human osteoblasts' response to Ti-6Al-4V implants in vitro.

Osseointegrated implants are a common therapy for the elderly population as lifespan increases. Understanding the effects of age and sex on osseointegration is important for successful implant therapy. Therefore, the response of primary human osteoblasts (HOB) to implant materials was studied. HOBs were obtained by outgrowth of cells from bone from orthopaedic procedures and categorized as Young (Y), <15; Middle (M), 30-50; and Old (O), >60 years old. Initially the HOB phenotype was determined on tissue culture plastic. Alkaline phosphatase (ALP) staining and activity were significantly increased in HOBs from older patients. Message levels of type I collagen (COL), bone sialoprotein (BSP) and ALP were significantly higher (from 2.3- to 3.8-fold) in Y subjects compared to M and O patients at 2 weeks. Studies of the response of HOBs to implant materials were undertaken using Ti-6Al-4V disks prepared in a manner similar to orthopaedic implants. A 1.4-fold (p<0.05) increase in cell attachment was found in HOBs from Y compared with O in female subjects but not in male subjects. Cell proliferation at 24 h was not significantly different by age or sex, nor was DNA content different at 2 and 4 weeks. Mineralization in HOB-implant cultures was 2.3-fold higher in Y than in O, and 1.7-fold higher in Y compared to M HOBs from female but not male subjects at 4 weeks. Northern blot and RT-PCR analysis at 2 weeks of culture showed significantly higher levels (1.6-2.3-fold) of COL, BSP, and osteocalcin (OC) mRNAs in Y HOBs compared to M and O HOBs from female subjects. We conclude that human osteoblasts from older female patients have a decreased ability to form bone on implants.