Bone Mineral Density and the Risk of Hip and Knee Osteoarthritis: The Johnston County Osteoarthritis Project

Objective

To address knowledge gaps regarding the relationship between bone mineral density (BMD) and incident hip or knee osteoarthritis (OA); specifically, lack of information regarding hip OA or symptomatic outcomes.

Methods

Using data (n = 1,474) from the Johnston County Osteoarthritis Project's first (1999–2004) and second (2005–2010) followup of participants ages ≥45 years, we examined the association between total hip BMD and both hip and knee OA. Total hip BMD was measured using dual x‐ray absorptiometry, and participants were classified into sex‐specific quartiles (low, intermediate low, intermediate high, and high). Radiographic OA (ROA) was defined as development of Kellgren/Lawrence grade ≥2. Symptomatic ROA (sROA) was defined as onset of both ROA and symptoms. Weibull regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

Median followup time was 6.5 years (range 4.0–10.2 years). In multivariate models, and compared with participants with low BMD, those with intermediate high and high BMD were less likely to develop hip sROA (HR 0.52 [95% CI 0.31–0.86] and 0.56 [95% CI 0.31–0.86], respectively; P = 0.024 for trend); high BMD was not associated (HR 0.69 [95% CI 0.45–1.06]) with risk of hip ROA. Compared with participants with low BMD, those with intermediate low and intermediate high total hip BMD were more likely to develop knee sROA (HR 2.15 [95% CI 1.40–3.30] and 1.65 [95% CI 1.02–2.67], respectively; P = 0.325 for trend); similar associations were seen with knee ROA.

Conclusion

Our findings suggest that higher BMD may reduce the risk of hip sROA, while intermediate levels may increase the risk of both knee sROA and ROA.

     

Incidence and risk factors of prosthetic joint infection after total hip or knee replacement in patients with rheumatoid arthritis

Objective

Prosthetic joint infection is one of the most dreaded complications after total joint arthroplasty, a common procedure in patients with rheumatoid arthritis (RA). We conducted a study to evaluate potential risk factors of prosthetic joint infection and to clarify if RA is an independent predictor of this complication.

Methods

This study included all patients with RA who underwent total hip or knee replacement at the Mayo Clinic Rochester between January 1996 and June 2004. The association of potential risk factors with prosthetic joint infection was examined using Cox models. A matched cohort of patients with osteoarthritis (OA) was assembled to determine whether RA is an independent risk factor for prosthetic joint infection.

Results

We identified 462 patients with RA who underwent a total of 657 hip or knee replacements. Overall, 23 (3.7%) joint arthroplasties were complicated by an infection during a mean ± SD followup of 4.3 ± 2.4 years. Revision arthroplasty (hazard ratio [HR] 2.99, 95% confidence interval [95% CI] 1.02–8.75) and a previous prosthetic joint infection of the replaced joint (HR 5.49, 95% CI 1.87–16.14) were significant predictors of postoperative prosthetic joint infection. Comparison of RA patients with a matched cohort of OA patients identified an increased risk of prosthetic joint infections (HR 4.08, 95% CI 1.35–12.33) in patients with RA.

Conclusion

Patients with RA who undergo total hip or knee replacement are at increased risk of prosthetic joint infection, which is further increased in the setting of revision arthroplasty and a previous prosthetic joint infection. These findings highlight the importance of perioperative prophylactic measures and vigilance during the postoperative period.     

Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study

BACKGROUND: Oral contraceptive use increases risk for venous thromboembolism, but data on the effect of postmenopausal hormone therapy are limited. OBJECTIVE: To determine the effect of therapy with estrogen plus progestin on risk for venous thromboembolic events in postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 20 clinical centers in the United States. PARTICIPANTS: 2763 postmenopausal women younger than 80 years of age (mean age, 67 years) who had coronary heart disease but no previous venous thromboembolism and had not had a hysterectomy. INTERVENTION: Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in one tablet (n = 1380) or placebo that was identical in appearance (n = 1383). MEASUREMENTS: Documented deep venous thrombosis or pulmonary embolism. RESULTS: During an average of 4.1 years of follow-up, 34 women in the hormone therapy group and 13 in the placebo group experienced venous thromboembolic events (relative hazard, 2.7 [95% CI, 1.4 to 5.0] [P = 0.003]; excess risk, 3.9 per 1000 woman-years [CI, 1.4 to 6.4 per 1000 woman-years]; number needed to treat for harm, 256 [CI, 157 to 692]). In multivariate analysis, the risk for venous thromboembolism was increased among women who had lower-extremity fractures (relative hazard, 18.1 [CI, 5.4 to 60.4]) or cancer (relative hazard, 3.9 [CI, 1.6 to 9.4]) and for 90 days after inpatient surgery (relative hazard, 4.9 [CI, 2.4 to 9.8]) or nonsurgical hospitalization (relative hazard, 5.7 [CI, 3.0 to 10.8]). Risk was decreased with aspirin (relative hazard, 0.5 [CI, 0.2 to 0.8]) or statin use (relative hazard, 0.5 [CI, 0.2 to 0.9]). CONCLUSIONS: Postmenopausal therapy with estrogen plus progestin increases risk for venous thromboembolism in women with coronary heart disease. This risk should be considered when the risks and benefits of therapy are being weighed.     

An age-related decrease in creatinine clearance is associated with an increase in number of falls in untreated women but not in women receiving calcitriol treatment

CONTEXT: Decreased calcitriol production due to impaired renal function may be a significant risk factor for falls in normal aging population. OBJECTIVE: The objective of the study was to examine the association between creatinine clearance (CrCl) and the incidence of falls and fallers in groups treated with placebo, calcitriol, estrogen therapy (ET)/estrogen + progestin therapy (HT), and calcitriol + ET/HT. DESIGN: This was a 3-yr, double-blind, placebo-controlled study designed to test the efficacy of calcitriol and ET/HT on bone loss and falls with analysis by intention to treat and post hoc. SETTING: The study was conducted at an academic outpatient center. PARTICIPANTS: Four hundred eighty-nine normal elderly women aged 65-77 yr; 415 women completed the study. INTERVENTION: Subjects were randomized to placebo, calcitriol 0.25 mug twice a day, ET daily (conjugated equine estrogens 0.625 mg), HT (conjugated equine estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg) and calcitriol + ET/HT. MAIN OUTCOME MEASURES: Cumulative number of falls and fallers were compared between groups with 24-h urine CrCl less than 60 and 60 ml/min or greater. RESULTS: Calcitriol treatment decreased the number of fallers and falls. Low CrCl less than 60 ml/min was a predictor of the number of falls per person but not fallers in the placebo group (P = 0.007). In the low CrCl group (<60 ml/min), the rate of falls decreased on calcitriol by 53% [95% confidence interval (CI) -71% to -22%; P = 0.003], calcitriol + ET/HT by 61% (95% CI -76% to -37%; P = 0.001), and ET/HT by 25% (95% CI: -55% to +24%; not significant). Calcitriol reduced the rate of falls by 30% (95% CI -49% to -4%; P = 0.027) in the CrCl 60 ml/min or greater group. CONCLUSION: Calcitriol treatment decreases falls in all subjects but especially in elderly women with decreased renal function (<60 ml/min) and frequent fallers.     

Postthrombotic syndrome after hip or knee arthroplasty: a cross-sectional study

BACKGROUND: Although the incidence of the postthrombotic syndrome (PTS) has been addressed in patients with symptomatic deep vein thrombosis (DVT), less information is available on the incidence in patients who develop asymptomatic DVT after major hip or knee arthroplasty. OBJECTIVES: To determine whether symptomatic PTS occurs more frequently in patients who develop DVT after hip or knee arthroplasty than those who are free of DVT and to provide an estimate of the incidence of PTS in patients who had undergone major hip or knee arthroplasty and had proximal DVT, distal (calf) DVT, or no DVT. DESIGN AND SETTING: A cross-sectional study conducted at the Hamilton Health Sciences Corporation, Hamilton, Ontario, and the Academic Medical Centre, Amsterdam, the Netherlands. SUBJECTS AND METHODS: Two hundred fifty-five subjects who had undergone major hip or knee arthroplasty 2 to 7 years previously and had routine predischarge venography showing proximal DVT (n = 25), distal DVT (n = 66), or no DVT (n = 164) were enrolled from March 1993 through December 1998. The presence of symptomatic PTS confirmed by the presence of objectively confirmed venous valvular incompetence was ascertained. RESULTS: The rates of PTS were low and not significantly different among the 3 subgroups: 1 (4.0%, 95% confidence interval [CI] = 0.1%-20.4%) of 25 patients with proximal DVT, 4 (6.1%, 95% CI = 1.7%-14.8%) of 66 patients with distal DVT, and 7 (4.3%, 95% CI = 1.7%-8.6%) of 164 patients with no DVT. CONCLUSIONS: Symptomatic PTS is an uncommon complaint after major hip or knee arthroplasty. Patients who develop postoperative proximal or distal DVT and who receive 6 to 12 weeks of anticoagulant therapy are not predisposed to PTS.     

Joint injury in young adults and risk for subsequent knee and hip osteoarthritis

BACKGROUND: Knee and hip injuries have been linked with osteoarthritis in cross-sectional and case-control studies, but few prospective studies have examined the relation between injuries in young adults and risk for later osteoarthritis. OBJECTIVE: To prospectively examine the relation between joint injury and incident knee and hip osteoarthritis. DESIGN: Prospective cohort study. SETTING: Johns Hopkins Precursors Study. PARTICIPANTS: 1321 former medical students. MEASUREMENTS: Injury status at cohort entry was recorded when the mean age of participants was 22 years. Injury during follow-up and incident osteoarthritis were determined by using self-administered questionnaires. Osteoarthritis was confirmed by symptoms and radiographic findings. RESULTS: Over a median follow-up of 36 years, 141 participants reported joint injuries (knee alone [n = 111], hip alone [n = 16], or knee and hip [n = 14]) and 96 developed osteoarthritis (knee alone [n = 64], hip alone [n = 27], or knee and hip [n = 5]). The cumulative incidence of knee osteoarthritis by 65 years of age was 13.9% in participants who had a knee injury during adolescence and young adulthood and 6.0% in those who did not (P = 0.0045) (relative risk, 2.95 [95% CI, 1.35 to 6.45]). Joint injury at cohort entry or during follow-up substantially increased the risk for subsequent osteoarthritis at that site (relative risk, 5.17 [CI, 3.07 to 8.71] and 3.50 [CI, 0.84 to 14.69] for knee and hip, respectively). Results were similar for persons with osteoarthritis confirmed by radiographs and symptoms. CONCLUSIONS: Young adults with knee injuries are at considerably increased risk for osteoarthritis later in life and should be targeted in the primary prevention of osteoarthritis.     

Racial/ethnic differences in surgical outcomes in veterans following knee or hip arthroplasty

OBJECTIVE: The utilization of joint arthroplasty for knee or hip osteoarthritis varies markedly by patient race/ethnicity. Because of concerns about surgical risk, black patients are less willing to consider this treatment. There are few published race/ethnicity-specific data on joint arthroplasty outcomes. The present study was undertaken to examine racial/ethnic differences in mortality and morbidity following elective knee or hip arthroplasty. METHODS: Using information from the Veterans Administration National Surgical Quality Improvement Program database, data on 12,108 patients who underwent knee arthroplasty and 6,703 patients who underwent hip arthroplasty over a 5-year period were analyzed. Racial/ethnic differences were determined using prospectively collected data on patient characteristics, procedures, and short-term outcomes. The main outcome measures were risk-adjusted 30-day mortality and complication rates. RESULTS: Adjusted rates of both non-infection-related and infection-related complications after knee arthroplasty were higher among black patients compared with white patients (relative risk [RR] 1.50, 95% confidence interval [95% CI] 1.08-2.10 and RR 1.42, 95% CI 1.06-1.90, respectively). Hispanic patients had a significantly higher risk of infection-related complications after knee arthroplasty (RR 1.64, 95% CI 1.08-2.49) relative to otherwise similar white patients. Race/ethnicity was not significantly associated with the risk of non-infection-related complications (RR 0.97, 95% CI 0.68-1.38 in blacks; RR 1.18, 95% CI 0.60-2.30 in Hispanics) or infection-related complications (RR 1.27, 95% CI 0.91-1.78 in blacks; RR 1.22, 95% CI 0.63-2.36 in Hispanics) after hip arthroplasty. The overall 30-day mortality was 0.6% following knee arthroplasty and 0.7% following hip arthroplasty, with no significant differences by race/ethnicity observed for either procedure. CONCLUSION: Although absolute risks of complication are low, our findings indicate that, after adjustment, black patients have significantly higher rates of infection-related and non-infection-related complications following knee arthroplasty, compared with white patients. In addition, adjusted rates of infection-related complications after knee arthroplasty are higher in Hispanic patients than in white patients. Such differences between ethnic groups are not seen following hip arthroplasty. These groups do not appear to differ significantly in terms of post-arthroplasty mortality rates.     

Association of new-onset breast discomfort with an increase in mammographic density during hormone therapy

BACKGROUND: Postmenopausal use of estrogen and progestin therapy increases breast density and breast discomfort. Whether this increase in breast density is heralded by new-onset breast discomfort is unknown. METHODS: We used data from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study, which retrieved and examined baseline and 12-month mammograms for 594 (67.9%) of 875 women aged 45 to 64 years enrolled in the randomized controlled trial. Treatments included placebo, 0.625 mg/d of conjugated equine estrogens, 0.625 mg/d of conjugated equine estrogens and medroxyprogesterone acetate (10 mg/d for 12 d/mo or 2.5 mg/d continuously), or 0.625 mg/d of conjugated equine estrogens and 200 mg/d of micronized progestin for 12 d/mo. Breast density (the percent of the breast composed of dense tissue) was calculated from digitized mammograms obtained at baseline and at 12-month follow-up. Breast discomfort was ascertained at baseline and at follow-up using standardized self-report questionnaires. In bivariate analysis, and then in multivariable linear regression models, we assessed the association between change in percent breast density from baseline to 12-month follow-up and new-onset breast discomfort in participants who had no breast discomfort at baseline (N = 533). RESULTS: After adjustment for age, treatment assignment (placebo, conjugated equine estrogens, or progestin-containing regimen), and other potential confounders, women with new-onset breast discomfort had a 3.9% increase in percent breast density compared with a 0.6% increase in percent breast density among women without new-onset breast discomfort (beta = .033, P<.001). The association between incident breast discomfort and increased percent breast density was similar in all active treatment arms. CONCLUSION: In postmenopausal women randomly assigned to menopausal hormone therapy vs placebo, new-onset breast discomfort is associated with increased mammographic density.     

Progression of radiographic hip osteoarthritis over eight years in a community sample of elderly white women

OBJECTIVE: To describe progression over 8 years in a community-based sample of elderly women with radiographic findings of hip osteoarthritis (RHOA) with or without hip pain. METHODS: Baseline and followup anteroposterior pelvic radiographs were obtained at a mean +/- SD 8.3 +/- 0.4 years of followup in women age > or =65 years at the baseline examination of the Study of Osteoporotic Fractures. We evaluated progression in 936 hips of 745 women with one or more baseline findings of RHOA: summary OA grade > or =2, minimum joint space (MJS) < or =1.5 mm, definite femoral or acetabular osteophytes, definite superolateral joint space narrowing (JSN), or moderate or worse superomedial JSN. We separately examined progression in hips with an MJS between 1.5 mm and 2.5 mm. Hip pain and lower extremity disability were assessed by questionnaire and examination. Measures of progression included an increase in summary grade of radiographic findings, increase in total osteophyte score, decrease in MJS of > or =0.5 mm, total hip replacement (THR), and increase in lower extremity disability score. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for baseline radiographic predictors of progression were estimated using general estimating equations. RESULTS: During followup, 12.9% of women with baseline RHOA underwent THR, and 22.8% had substantial worsening of lower extremity disability, while 64.6% of hips with RHOA showed radiographic progression or were replaced. Progression was greater by all measures in the 37% of hips and 47% of women with both RHOA and hip pain at baseline. Of hips with pain, 23.6% progressed to THR compared with 2.7% of hips without pain (OR 8.1 [95% CI 4.2, 15.4], P < 0.001), and MJS decreased > or =0.5 mm in 53.7% of hips with pain compared with 30.7% of hips without pain (OR 1.9 [95% CI 1.4, 2.6], P < 0.001). Women with hip pain were more likely to have worsened lower extremity disability (29.3% versus 17.6%; OR 1.8 [95% CI 1.2, 2.8], P = 0.0053). Hips with an MJS >1.5 mm and < or =2.5 mm (n = 1,868) had primarily superomedial narrowing and comparatively low rates of progression that did not differ by hip pain. Femoral osteophytes, superolateral JSN, and subchondral bone changes were independent predictors of progression. CONCLUSION: Among women recruited from the community, radiographic and clinical progression was greater in those with symptomatic RHOA, but still substantially less frequent than previously reported for hip OA patients in clinical settings. Asymptomatic RHOA and hips with an isolated finding of mild JSN (MJS of 1.5 mm to 2.5 mm) were unlikely to progress over 8 years.     

Patient race and surgical outcomes after total knee arthroplasty: An analysis of a large regional database

Objective

To examine racial differences in surgical complications, mortality, and revision rates after total knee arthroplasty.

Methods

We studied patients undergoing primary total knee arthroplasty using 2001–2007 Pennsylvania Health Care Cost Containment Council data. We conducted bivariate analyses to assess the risk of complications such as myocardial infarction, venous thromboembolism, wound infections, and failure of prosthesis, as well as 30‐day and 1‐year overall mortality after elective total knee arthroplasty, between racial groups. We estimated Kaplan‐Meier 1‐ and 5‐year surgical revision rates, and fit multivariable Cox proportional hazards models to compare surgical revision by race, incorporating 5 years of followup. We adjusted for patient age, sex, length of hospital stay, surgical risk of death, type of health insurance, hospital surgical volume, and hospital teaching status.

Results

In unadjusted analyses, there were no significant differences by racial group for either overall 30‐day or in‐hospital complication rates, or 30‐day and 1‐year mortality rates. Adjusted Cox models incorporating 5 years of followup showed an increased risk of revisions for African American patients (hazard ratio [HR] 1.39, 95% confidence interval [95% CI] 1.08–1.80), younger patients (HR 2.30, 95% CI 1.96–2.69), and lower risk for female patients (HR 0.81, 95% CI 0.71–0.92).

Conclusion

In this sample of patients who underwent knee arthroplasty, we found no significant racial differences in major complication rates or mortality. However, African American patients, younger patients, and male patients all had significantly higher rates of revision based on 5 years of followup.     

Effects of nosocomial candidemia on outcomes of critically ill patients

PURPOSE: To determine whether nosocomial candidemia is associated with increased mortality in intensive care unit (ICU) patients. SUBJECTS AND METHODS: We performed a retrospective (1992 to 2000) cohort study of 73 ICU patients with candidemia and 146 matched controls. Controls were matched based on disease severity as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (+/- 1 point), diagnostic category, and length of ICU stay before onset of candidemia. RESULTS: In comparison with the control group, patients with candidemia developed more acute respiratory failure (97% [n = 71] vs. 88% [n = 129], P = 0.03) during their ICU stay. They were mechanically ventilated for a longer period (29 +/- 26 days vs. 19 +/- 19 days, P<0.01) and had a longer stay in the ICU (36 +/- 33 days vs. 25 +/- 23 days, P = 0.02) as well as in the hospital (77 +/- 81 days vs. 64 +/- 69 days, P = 0.04). There was no difference in in-hospital mortality between the groups (48% [n = 35] vs. 43% [n = 62], P = 0.44), a difference of 5% (95% confidence interval [CI]: -8% to 19%). In a multivariate analysis, older age (hazard ratio [HR] = 1.13 per 10 years; 95% CI: 1.04 to 1.23; P = 0.004), acute renal failure (HR = 1.4; 95% CI: 1.1 to 2.0; P = 0.02), and unfavorable APACHE II scores (HR = 1.10 per 5 points; 95% CI: 1.00 to 1.20; P = 0.05) were independent predictors of mortality. Candidemia was not associated with mortality in a model that adjusted for these factors (HR = 0.9; 95% CI: 0.7 to 1.2; P = 0.53). CONCLUSION: Nosocomial candidemia does not adversely affect the outcome in ICU patients in whom mortality is attributable to age, the severity of underlying disease, and acute illness.     

Effects of hormone replacement therapy on clinical fractures and height loss: The Heart and Estrogen/Progestin Replacement Study (HERS)

PURPOSE: To determine if estrogen plus progestin reduces the incidence of fractures or height loss in postmenopausal women with coronary disease. SUBJECTS AND METHODS: We enrolled 2,763 postmenopausal women with coronary disease and with an intact uterus into the Heart Estrogen/progestin Replacement Study, a randomized double-blind, placebo-controlled secondary prevention trial of cardiovascular disease. Radiographically documented clinical fractures were a prespecified secondary endpoint. Height loss was used as a surrogate for vertebral fractures. The average age of the women was 66.7 +/- 6.7 years, and fewer than 15% of the women had osteoporosis based on their bone density. Women were randomly assigned to either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n = 1,380) or placebo (n = 1,383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 64% at the end of the study. RESULTS: During 10,554 person years of follow-up, 286 women experienced a fracture: 138 in the treatment group (26.3 per 1,000 person years) and 148 in the placebo group (28.0 per 1,000 person years); relative hazard, 0.94; 95% confidence interval 0.8 to 1.2, P = 0.61). These included 58 wrist fractures (1.01; 0.6 to 1.7); 27 hip fractures (1.09; 0.5 to 2.3); 32 spine fractures (0.69; 0.3 to 1.4), and 192 other fractures (0.91; 0.7 to 1.2). There was no difference in average height loss between the treatment and placebo groups or in the percent of women who lost more than 2 cm in height: 10.6% in the treatment group and 12.1% in the placebo group. CONCLUSIONS: There was no evidence of a reduction in the incidence of fractures or rate of height loss in older women not selected for osteoporosis. Randomized studies are needed to clarify the effect of hormone replacement therapy on fracture risk among women with and without osteoporosis.     

Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan

BACKGROUND: An association between diabetes mellitus (DM) and cancer has long been speculated, but no conclusive evidence has been obtained. METHODS: We prospectively examined the association between a history of DM and subsequent risk of cancer in the Japan Public Health Center-Based Prospective Study. A total of 97 771 general Japanese persons (46 548 men and 51 223 women) aged 40 to 69 years who responded to the baseline questionnaire, from January 1990 to December 1994, were followed up for cancer incidence through December 31, 2003. At baseline, 6.7% of men and 3.1% of women had a history of DM. RESULTS: A total of 6462 cases of newly diagnosed cancer were identified. In men, a 27% increase in the risk of total cancer incidence was observed in those with a history of DM (n = 3907 [366 with DM]; hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.14-1.42). The HR was especially high for those with cancer of the liver (n = 312 [52 with DM]; HR, 2.24; 95% CI, 1.64-3.04), pancreas (n = 118 [16 with DM]; HR, 1.85; 95% CI, 1.07-3.20), and kidney (n = 99 [13 with DM]; HR, 1.92; 95% CI, 1.06-3.46). We also observed a moderately increased risk of colon cancer (n = 491 [46 with DM]; HR, 1.36; 95% CI, 1.00-1.85) and of stomach cancer with borderline significance (n = 977 [87 with DM]; HR, 1.23; 95% CI, 0.98-1.54). In women, a borderline significant increase in risk was observed for the incidence of total cancer (n = 2555 [104 with DM]; HR, 1.21; 95% CI, 0.99-1.47), while statistical significance was observed for the incidence of stomach cancer (n = 362 [20 with DM]; HR, 1.61; 95% CI, 1.02-2.54) and liver cancer (n = 120 [10 with DM]; HR, 1.94; 95% CI, 1.00-3.73) and borderline significance was observed for the incidence of ovarian cancer (n = 74 [5 with DM]; HR, 2.42; 95% CI, 0.96-6.09). CONCLUSION: Patients with DM drawn from the general Japanese population may be at increased risk of total cancer and of cancer in specific sites.     

Deletion of chromosome band 13q14 as detected by fluorescence in situ hybridization is a prognostic factor in patients with multiple myeloma who are receiving allogeneic dose-reduced stem cell transplantation

We investigated in a retrospective multicenter study the impact of chromosome arm 13q deletion (13q-) as detected by fluorescence in situ hybridization (FISH) on outcome after dose-reduced allografting in patients with multiple myeloma. In 68 of 140 patients, data on chromosome 13q status were available. Most patients included had advanced myeloma. At 2 years, patients with 13q deletion (n = 31) had a shorter event-free (18% vs 42%; P =.05) and overall survival (18% vs 67%; P =.03) than patients without 13q- (n = 37). Patients with 13q- experienced a higher relapse rate (77% vs 44%; P <.001) but a similar incidence of transplantation-related mortality at one year (24% vs 18%). In a multivariate analysis, 13q- remained a significant risk factor for a higher relapse rate (hazard ratio [HR], 3.28; 95% confidence interval [CI], 1.31-8.24; P =.01) and a shorter event-free survival (HR, 1.94; 95% CI, 1.03-3.67; P =.04). Concerning overall survival, 2 or more cycles of prior high-dose chemotherapy were associated with a significantly higher probability of death (HR, 2.48; 95% CI, 1.19-5.17; P =.02), while patients with deletion 13q had a nearly 2 times higher risk of death (HR, 1.94; 95% CI, 0.95-3.98; P =.07) after dose-reduced allogeneic stem cell transplantation.     

Fracture risk among breast cancer survivors: results from the Women's Health Initiative Observational Study

BACKGROUND: Breast cancer and its treatment may compromise bone health. We tested the hypothesis in the Women's Health Initiative Observational Study that postmenopausal survivors of breast cancer have a higher risk for fractures compared with women who have no cancer history. METHODS: A prospective cohort (5.1 years' follow-up) study design was used. Breast cancer survivors were women who reported a history of breast cancer (n = 5298). A reference group included women who had no cancer history at baseline (n = 80 848). Fracture occurrence was ascertained from annual self-reports. Hip fractures were confirmed by reviewing medical records. RESULTS: After adjustment for age, weight, ethnicity, and geographic region of enrollment, the hazard ratios (HRs) of breast cancer survivors to women in the reference group were 0.93 (95% confidence interval [CI], 0.64-1.33) for hip; 1.36 (95% CI, 1.16-1.59) for forearm or wrist; 1.31 (95% CI, 1.19-1.43) for eligible fractures other than hip, vertebral, and forearm or wrist; and 1.31 (95% CI, 1.21-1.41) for these fractures combined. The increased risk for clinical vertebral fracture was statistically significant only among survivors who had a breast cancer diagnosis before age 55 years (HR, 1.78; 95% CI, 1.28-2.46). After adjusting for factors related to hormone levels, risk of fall, fracture history, medication use, comorbidity, and lifestyle, the increased risk for all fractures studied among survivors was reduced to 15% (HR, 1.15; 95% CI, 1.05-1.25). CONCLUSIONS: Postmenopausal survivors of breast cancer are at increased risk for clinical fractures. Preventions and therapeutic interventions are needed to reduce fracture risk in this large and growing population.     

Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study

We examined the prognostic impact of cytogenetics on the outcome of 200 acute lymphoblastic leukemia (ALL) patients 15 to 65 years of age enrolled in Southwest Oncology Group (SWOG)-9400 study. Evaluable cytogenetics or fluorescence in situ hybridization studies were available in 140 (70%) patients. Four karyotype categories (normal [n = 31, 22%], t(9;22)/BCR/ABL1 [n = 36, 26%], other unfavorable [-7, +8, or 11q23 rearrangement, n = 19, 13%], and miscellaneous [n = 54, 39%]) and the biologically and clinically relevant ALL ploidy subgroups were prospectively defined. Overall survival (OS) decreased significantly with increasing age (P = .009) and varied with karyotype category (P < .001). OS was worst for t(9;22)/BCR/ABL1 followed by other unfavorable karyotypes, with hazard ratios (HR) of 3.45 (95% confidence interval [CI], 1.88-6.31) and 2.14 (95% CI, 1.04-4.04), respectively, compared with normal diploid group. OS of the miscellaneous group was similar to that of the normal diploid group (HR = 0.82; 95% CI, 0.44-1.53). Relapse-free survival (RFS) was not significantly associated with age (P = .30) but was heterogeneous among karyotype categories (P < .001) primarily because of poor RFS in t(9;22)/BCR/ABL1 (HR = 3.49; 95% CI, 1.80-6.75) compared with the normal diploid group. After accounting for the variation among karyotype groups, age was not a significant prognostic factor for OS or RFS, highlighting cytogenetics as the most important prognostic factor in adult ALL. This trial was registered at www.ClinicalTrials.gov as #NCT00002665.     

Primary knee and hip arthroplasty among nonagenarians and centenarians in the United States

OBJECTIVE: The number of individuals ages >or=100 years in the US is expected to increase considerably in the future along with the need for arthroplasties. This report focuses on the poorly studied epidemiology and mortality outcomes of arthroplasty among these individuals. METHODS: We describe the epidemiology of knee and hip arthroplasties among centenarians using data from a large hospital discharge database in the US (the Nationwide Inpatient Sample) during the period 1993 through 2002. We used nonagenarians as the comparison group with adjustment for differences in the prevalence of congestive heart failure, neurologic diseases such as dementia and stroke, renal and hepatic diseases, obesity, anemia, malignancy, coagulopathy, and depression and other psychiatric illnesses. Cox regression models were used to study the mortality outcomes following arthroplasty. RESULTS: Overall, there were 679 hip arthroplasties and 7 knee arthroplasties among centenarians in this database. The corresponding figures for nonagenarians were 33,975 and 2,050, respectively. A vast majority (83%) of hip arthroplasty recipients were women. Risk-adjusted mortality estimates following arthroplasty for centenarians were higher than for nonagenarians (hazard ratio 1.46, 95% confidence interval 1.10-1.95). However, this was similar to differences in overall in-hospital mortality (hazard ratio 1.36, 95% confidence interval 1.32-1.40) between these 2 age categories. CONCLUSION: In the US population, hip and knee arthroplasty are very rarely performed among centenarians. Our in-hospital mortality data suggest that arthroplasties should not be denied to centenarians solely because of short-term postoperative life expectancy estimates.     

The impact of body mass index on later total hip arthroplasty for primary osteoarthritis: a cohort study in 1.2 million persons

OBJECTIVE: To investigate the effects of body mass index (BMI), height, and age on the risk of later total hip arthroplasty for primary osteoarthritis (OA). METHODS: We matched screening data on body height and weight from 1,152,006 persons ages 18-67 years who attended a compulsory screening for tuberculosis in 1963-1975 with data from the Norwegian Arthroplasty Register for the years 1987-2003. We identified 28,425 total hip replacements because of primary OA. RESULTS: We found dose-response associations between both height and BMI and later hip arthroplasty. The relative risk (RR) among men with a BMI > or = 32 kg/m2 versus a BMI of 20.5-21.9 kg/m2 was 3.4 (95% confidence interval [95% CI] 2.9-4.0). The corresponding RR in women was 2.3 (95% CI 2.1-2.4). There was a decreasing trend in the RR with an increasing age at screening. Among men, the RR for an increase of 5 kg/m2 in the BMI was 2.1 (95% CI 1.7-2.5) when measured at age <25 years and 1.5 (95% CI 1.3-1.7) when measured at ages 55-59 years. Among women, the corresponding RR values were 1.7 (95% CI 1.5-1.9) and 1.1 (95% CI 1.1-1.2). CONCLUSION: There was a strong dose-response association between BMI and later total arthroplasty for OA of the hip. Being overweight entailed the highest RR among young participants, and the participants who were overweight at a young age maintained an excess RR for arthroplasty throughout the followup period.     

Presence of peripheral arthritis and male sex predicting continuation of anti–tumor necrosis factor therapy in ankylosing spondylitis: An observational prospective cohort study from the South Swedish arthritis treatment group register

Objective

To examine clinical characteristics as possible predictors of long‐term treatment continuation with adalimumab, etanercept, and infliximab in ankylosing spondylitis (AS) patients who had never taken biologics treated in clinical practice.

Methods

Patients in southern Sweden with active AS starting biologic therapy for the first time between October 1999 and December 2008 (n = 243, 75% men) were included in a structured clinical followup over 2 years. Patients with clinical spondylitis had not responded to at least 2 nonsteroidal antiinflammatory drugs, whereas patients who also had peripheral arthritis (n = 121) had additionally failed at least 1 conventional disease‐modifying antirheumatic drug (DMARD) treatment course. The mean ± SD age at inclusion was 43 ± 12 years, with a mean ± SD disease duration prior to treatment of 16 ± 12 years.

Results

The 2‐year drug continuation rate was 74%. Male sex (hazard ratio [HR] of premature discontinuation 0.36 [95% confidence interval (95% CI) 0.19–0.68]) and the presence of peripheral arthritis (HR 0.49 [95% CI 0.27–0.88]) were found to be significant predictors of better drug survival. Furthermore, a trend was seen for more favorable drug continuation on treatment with etanercept as compared with infliximab (HR 0.50 [95% CI 0.25–1.04], P = 0.062), whereas no differences were found comparing the 3 anti–tumor necrosis factor agents in other ways. Higher baseline C‐reactive protein level (HR 0.99 [95% CI 0.97–1.00], P = 0.12) and concomitant treatment with nonbiologic DMARDs (HR 0.61 [95% CI 0.34–1.10], P = 0.10) also showed trends to entail better drug adherence.

Conclusion

AS patients in this study have an excellent 2‐year drug survival rate of 74%. Significant predictors for treatment continuation in this study were male sex and the presence of peripheral arthritis.     

Does medication adherence itself confer fracture protection? An investigation of the healthy adherer effect in observational data

Objective

Prior observational studies have shown an association between bisphosphonate adherence and fewer fractures. It is unclear if such studies reflect pharmacologic benefits or behavioral attributes, i.e., the healthy adherer effect. Our objective was to examine the association of therapy adherence and fracture risk among patients initiating therapies hypothesized to be favorable, unfavorable, or neutral toward fracture risk, in order to evaluate for a healthy adherer effect.

Methods

In this observational study, we identified patients within Medicare 2006–2009 data who initiated any of 3 medication groups within 9 months after an osteoporotic fracture as follows: 1) oral bisphosphonates (n = 2,507), 2) selective serotonin reuptake inhibitors (SSRIs; n = 2,420), or 3) angiotensin‐converting enzyme (ACE) inhibitor or calcium‐channel blocker (CCB; n = 2,178). Cox regression analysis, adjusting for covariates, was used to compare fracture rates at the hip and major osteoporotic fracture sites (including hip, clinical vertebral, humerus, and wrist) during followup, comparing patients with high adherence versus low adherence within each medication group.

Results

There were few baseline differences between those who had high adherence versus lower adherence. High adherence with bisphosphonates decreased fracture risk at both hip (hazard ratio [HR] 0.53, 95% confidence interval [95% CI] 0.32–0.96) and major fracture sites (HR 0.61, 95% CI 0.45–0.80). High adherence with SSRIs suggested increased fracture risk at both hip (HR 1.58, 95% CI 0.97–2.57) and major fracture sites (HR 1.32, 95% CI 0.96–1.83). High adherence with ACE inhibitors/CCBs was neutral toward fracture risk at both hip (HR 1.27, 95% CI 0.67–2.41) and major fracture sites (HR 1.00, 95% CI 0.67–1.49).

Conclusion

In this observational cohort of older individuals, the association between medication adherence and fracture risk differed by medication exposure, suggesting a limited role for the healthy adherer effect in observational studies of osteoporosis medications.