Outcomes of Patients With Diffuse Systemic Sclerosis Eligible for Autologous Stem Cell Transplantation Treated With Conventional Therapy.

OBJECTIVE: The study objective was to determine the event-free survival (EFS) of Australian patients with diffuse cutaneous systemic sclerosis (dcSSc) who met eligibility criteria for autologous stem cell transplant (ASCT) in previously published randomized controlled trials but were not treated with ASCT. METHODS: Patients who met inclusion criteria for the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) and Scleroderma: Cyclophosphamide Or Transplantation (SCOT) trials were identified from the multicenter Australian Scleroderma Cohort Study (ASCS). EFS (survival without cardiac, renal, or pulmonary failure or death) at 4 years was assessed. ASCS patients who had already undergone transplantation were excluded from analysis. RESULTS: Of the 492 patients with dcSSc in the ASCS, 56 met ASTIS inclusion criteria for ASCT (56 of 492 [11.4%]) and 30 met SCOT inclusion criteria (30 of 492 [6.1%]). An additional 11 patients met ASTIS or SCOT inclusion criteria, but they were excluded due to severe organ manifestations. EFS at 4 years in ASCS patients meeting ASTIS inclusion criteria was 83.3% and in ASCS patients meeting SCOT inclusion criteria was 81.2%. EFS at 4 years in ASCS patients who met ASTIS and SCOT inclusion but also exclusion criteria was 46.7% and 45.7%, respectively. CONCLUSION: ASCS patients meeting ASTIS and/or SCOT inclusion criteria who were not treated with ASCT have similar EFS at 4 years as patients receiving ASCT and better EFS than those receiving cyclophosphamide in the ASTIS and SCOT trials. This may reflect confounders unable to be controlled for, including survivor bias, but may also reflect improved standard of care for dcSSc over time.

Large-vessel vasculitis in graft-versus-host disease: a case report.

BACKGROUND: Graft-versus-host disease is a common complication seen with allogenic stem cell transplant, which is used to treat a variety of hematological malignancies. Graft-versus-host disease is an allogenic syndrome and can present in a variety of ways, including symptoms mimicking various autoimmune diseases; however, it is quite rare to see graft-versus-host disease affecting the vascular system and causing vasculitis. CASE PRESENTATION: We describe a case of a 59-year-old Caucasian man with follicular lymphoma and diffuse large B-cell transformation who developed graft-versus-host disease post allogenic hematopoietic stem cell transplantation and later progressed to neurological complication foot drop and large-vessel vasculitis. CONCLUSION: The life-threatening vascular complications associated with large-vessel vasculitis include arterial aneurysms and dissections, and ischemic or hemorrhagic stroke. Thus, this rare immunological association needs to be recognized and treated in a timely manner to prevent the long-term complications.

Knee and hip radiographic osteoarthritis predict total hip bone loss in older adults: a prospective study.

The relationship between osteoarthritis (OA) and osteoporosis remains controversial. This study was designed to determine the association between hip and knee radiographic OA and change in total hip bone mineral density (BMD) over 2.6 years. A total of 867 population-based randomly selected subjects (mean age 62 years, range 51 to 80 years, and 49% female) were included. Hip and knee joint space narrowing (JSN, 0 to 3) and osteophytes (0 to 3) in both lower limbs was assessed using Altman's atlas. Total hip BMD was measured by dual-energy X-ray absorptiometry (DXA). We found that radiographic OA (score of JSN or osteophytes > 0) was common in this sample (hip 45%, knee 68%). In multivariable analyses, percentage change in total hip BMD per year was predicted by right and left hip axial JSN (beta = -0.25% and -0.29% per grade, respectively, both p < .05), right hip superior femoral osteophytes (grades 2 and 3 versus 0: beta = -1.60, p < .05), combined right and left knee tibiofemoral JSN (beta = -0.06 per grade from grades 0 to 12, p < .05), and osteophytes (beta = -0.06 per grade from grades 0 to 14, p < .05) independent of each other and joint pain. In conclusion, older subjects with radiographic hip and knee OA have higher total hip bone loss over 2.6 years regardless of symptoms, suggesting that consideration should be given to the monitoring of bone mass in these subjects.

Correlates of knee pain in older adults: Tasmanian Older Adult Cohort Study.

OBJECTIVE: To describe the association between chondral defects, bone marrow lesions, knee and hip radiographic osteoarthritis (OA), and knee pain. METHODS: Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index. T1- and T2-weighted fat saturation magnetic resonance imaging was performed on the right knee to assess chondral defects and subchondral bone marrow lesions. Radiography was performed on the right knee and hip and scored for radiographic OA. Body mass index (BMI) and knee extension strength were measured. RESULTS: A total of 500 randomly selected men and women participated. The prevalence of knee pain was 48%. In multivariable analysis, prevalent knee pain was significantly associated with medial tibial chondral defects (odds ratio [OR] 2.32, 95% confidence interval [95% CI] 1.02-5.28 for grade 3 versus grade 2 or less; OR 4.93, 95% CI 1.07-22.7 for grade 4 versus grade 2 or less), bone marrow lesions (OR 1.44, 95% CI 1.04-2.00 per compartment), and hip joint space narrowing (OR 1.36, 95% CI 1.07-1.73 per unit), as well as greater BMI and lower knee extension strength. It was not significantly associated with radiographic knee OA. These variables were also associated with more severe knee pain. In addition, there was a dose response association between knee pain and number of sites having grade 3 or 4 chondral defects (OR 1.39, 95% CI 1.12-1.73 per site), with all subjects having knee pain if all compartments of the knee had these defects. CONCLUSION: Knee pain in older adults is independently associated with both full and non-full-thickness medial tibial chondral defects, bone marrow lesions, greater BMI, and lower knee extension strength, but is not associated with radiographic knee OA. The association between radiographic hip OA and knee pain indicates that referred pain from the hip needs to be considered in unexplained knee pain.

Natural history of knee cartilage defects and factors affecting change.

BACKGROUND: Knee cartilage defects may play an important role in early osteoarthritis, but little is known about their natural history. METHODS: Knee cartilage defect score (range, 0-4), cartilage volume, and bone surface area were determined using T1-weighted fat-saturated magnetic resonance imaging in 325 subjects (mean age, 45 years) at baseline and 2 years later. RESULTS: Thirty-three percent of the subjects had a worsening (>or=1-point increase) and 37% of the subjects had an improvement (>or=1-point decrease) in cartilage defect score in any knee compartment during 2.3 years. A worsening in cartilage defect score was significantly associated with female sex (odds ratio [OR], 3.09 and 3.64 in the medial and lateral tibiofemoral compartments) and baseline factors, including age (OR, 1.05 per year in the medial tibiofemoral compartment), body mass index (OR, 1.08 in the lateral tibiofemoral compartment), tibiofemoral osteophytes (OR, 6.22 and 6.04 per grade), tibial bone area (OR, 1.24 and 2.07 per square centimeter), and cartilage volume (OR, 2.91 and 1.71 per milliliter in the medial tibiofemoral and patellar compartments). An improvement in cartilage defect score had similar but reversed associations with these factors (except for sex), including a decrease in body mass index (OR, 1.23 in the medial tibiofemoral compartment). CONCLUSIONS: Knee cartilage defects are variable, and changes are associated with female sex, age, and body mass index. Increases are associated with baseline cartilage volume, bone size, and osteophytes, suggesting a role for these in the pathogenesis of cartilage defects. Interventions such as weight loss may improve knee cartilage defects.

The genetic contribution and relevance of knee cartilage defects: case-control and sib-pair studies.

OBJECTIVE: To describe the differences in knee cartilage defects between offspring of subjects with at least one parent with a total knee replacement for severe primary knee osteoarthritis (OA) and controls; and to estimate the heritability of knee cartilage defects in sib-pairs. METHODS: Population based, case-control study of 186 matched pairs (mean age 45 yrs, range 26-61) and sib-pair study of 128 subjects from 51 families (115 sib-pairs) within the case-control study. Knee cartilage defect scores (0-4) and prevalence (a cartilage defect score > or = 2) were assessed at the patellar, tibial, and femoral sites by processing images acquired using T1 weighted fat-saturated magnetic resonance imaging. Heritability was estimated using the SOLAR genetic analysis program. RESULTS: The prevalence of knee cartilage defects was surprisingly high (50% scored > or = 2 in any site). Compared to controls, offspring had higher knee cartilage defect scores and prevalence in tibiofemoral (4.39 vs 4.01, p = 0.003; 41% vs 28%, p = 0.009), patellar (1.32 vs 1.10, p = 0.031; 35% vs 26%, p = 0.075), and whole (5.71 vs 5.10, p = 0.002; 57% vs 42%, p = 0.007) compartments. These all became nonsignificant after adjustment for knee pain and radiographic OA. In the sib-pair component, knee cartilage defects had heritability for scores and prevalence, respectively, of 38% (p = 0.072) and 47% (p = 0.082) for tibiofemoral, 52% (p = 0.009) and 78% (p = 0.025) for patellar, and 43% (p = 0.038) and 68% (p = 0.072) for the whole compartments. These estimates became weaker at tibiofemoral and whole compartments after adjustment for bone size, knee pain, and radiographic OA. CONCLUSION: Knee cartilage defects are common, have a genetic component that is linked to the genetic contribution to knee pain and bone size, and may have a role in the genetic pathogenesis of knee OA.

Knee structural alteration and BMI: a cross-sectional study.

OBJECTIVE: To describe the associations among BMI, knee cartilage morphology, and bone size in adults. RESEARCH METHODS AND PROCEDURES: A cross-sectional convenience sample of 372 male and female subjects (mean age, 45 years; range, 26 to 61 years) was studied. Knee articular cartilage defect score (0 to 4) and prevalence (defect score of >/=2), volume, and thickness, as well as bone surface area and/or volume, were determined at the patellar, tibial, and femoral sites using T1-weighted fat-saturation magnetic resonance imaging. Height, weight, BMI, and radiographic osteoarthritis were measured by standard protocols. RESULTS: In multivariate analysis in the whole group, BMI was significantly associated with knee cartilage defect scores (beta: +0.016/kg/m(2) to +0.083/kg/m(2), all p < 0.05) and prevalence (odds ratio: 1.05 to 1.12/kg/m(2), all p < 0.05 except for the lateral tibiofemoral compartment). In addition, BMI was negatively associated with patellar cartilage thickness only (beta = -0.021 mm/kg/m(2); p = 0.039) and was positively associated with tibial bone area (medial: beta = +7.1 mm(2)/kg/m(2), p = 0.001; lateral: beta = +3.2 mm(2)/kg/m(2), p = 0.037). Those who were obese also had higher knee cartilage defect severity and prevalence and larger medial tibial bone area but no significant change in cartilage volume or thickness compared with those of normal weight. DISCUSSION: This study suggests that knee cartilage defects and tibial bone enlargement are the main structural changes associated with increasing BMI particularly in women. Preventing these changes may prevent knee osteoarthritis in overweight and obese subjects.

Factors associated with hip cartilage volume measured by magnetic resonance imaging: the Tasmanian Older Adult Cohort Study.

OBJECTIVE: To compare associations between anthropometric and lifestyle factors and femoral head cartilage volume/thickness and radiographic features of osteoarthritis (OA) and to provide evidence of construct validity for magnetic resonance imaging (MRI) assessment of femoral cartilage volume and thickness. METHODS: We studied a cross-sectional sample of 151 randomly selected subjects (79 men, 72 women; mean age 63 years) from the Tasmanian Older Adult Cohort Study. A sagittal T1-weighted fat-suppression MRI scan of the right hip was performed to determine femoral head cartilage volume, cartilage thickness, and size. An anteroposterior radiograph of the pelvis with weight bearing was performed and scored for radiographic evidence of OA in the right hip. Other factors measured were height, weight, leg strength, serum vitamin D levels, and bone mineral density. RESULTS: Hip cartilage volume was significantly associated with female sex, body mass index, and femoral head size, whereas hip cartilage thickness was significantly associated only with the size of the femoral head. Only female sex was significantly associated with the total radiographic OA score and the joint space narrowing (JSN) score, but not the osteophyte score. Radiographic JSN of the hip, especially axial JSN (but not osteophytes), was significantly correlated with hip cartilage volume and thickness. CONCLUSION: Femoral head cartilage volume and thickness have modest but significant construct validity when correlated with radiographic findings. Furthermore, the generally stronger associations with volume compared with radiographic OA suggest that MRI may be superior at identifying risk factors for hip OA.

Knee cartilage defects: association with early radiographic osteoarthritis, decreased cartilage volume, increased joint surface area and type II collagen breakdown.

OBJECTIVE: To generate hypotheses regarding the associations between knee cartilage defects and knee radiographic osteoarthritis (ROA), cartilage volume, bone size and type II collagen breakdown in adults. METHODS: A cross-sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26-61) was studied. Knee cartilage defect score (0-4) and prevalence (a defect score of > or =2), cartilage volume, and bone surface area were determined using T1-weighted fat saturation MRI. Urinary levels of C-terminal crosslinking telopeptide of type II collagen (U-CTX-II) were measured by enzyme-linked immunosorbent assay. Height, weight and ROA were measured by standard protocols. RESULTS: In multivariate analysis, the severity and prevalence of knee cartilage defects were significantly and independently associated with tibiofemoral osteophytes (regression coefficient (beta): +0.86 to +1.31/unit, odds ratio (OR): 2.97-3.68/unit, all P<0.05 with the exception of OR in lateral tibiofemoral compartment) and tibial bone area (beta: +0.11 to +0.25/cm2; OR: 1.33-1.58/cm2, all P<0.01). Knee cartilage defects were inconsistently associated with joint space narrowing after adjustment for osteophytes but consistently with knee cartilage volume (beta: -0.27 to -0.70/ml; OR: 0.16-0.56/ml, all P<0.01 except for OR at lateral tibial cartilage site P=0.06). Lastly, knee cartilage defect severity was significantly associated with U-CTX-II (Partial r=+0.18, P<0.001 for total cartilage defect score). CONCLUSION: Osteophytes and increasing knee bone size may be causally related to knee cartilage defects. Furthermore, knee cartilage defects may result in increased cartilage breakdown leading to decreased cartilage volume and joint space narrowing suggesting an important role for knee cartilage defects in early knee OA.

The association between hormonal and reproductive factors and hand osteoarthritis.

OBJECTIVE: To describe the association of reproductive and hormonal factors with the presence and severity of hand osteoarthritis (OA) in Tasmanian women. METHODS: Cross-sectional study of 348 women from 76 families. A structured questionnaire collected information regarding reproductive history and the use of estrogen containing medications. Hand OA was assessed by two observers using the Altman atlas for joint space narrowing and osteophytes at distal interphalangeal (DIP) and carpometacarpal (CMC) joints, as well as Heberden's nodes (HN) based on hand photography. RESULTS: The prevalence of hand OA was high in this sample at 65-70%. Parity, increasing age at menopause and years of menstruation were associated with both symptomatic hand OA and a more severe DIP score (but not presence of radiographic disease) while both current and ever use of hormone replacement therapy (HRT) were significantly associated with increased prevalence of HN and severity of HN and DIP OA (all P<0.05). HRT usage less than 5 years was associated with increased severity of both DIP disease and HN. No factors were associated with CMC disease apart from ever breast-feeding which was protective (OR 0.37, 95% CI 0.18-0.79). CONCLUSIONS: These results require confirmation in clinical trials or carefully controlled longitudinal studies but suggest that estrogen exposure around the time of disease onset (either endogenous or exogenous) may have a "priming" effect on the severity of DIP OA while breast-feeding in earlier life may be protective for CMC OA.

A cross sectional study of the association between sex, smoking, and other lifestyle factors and osteoarthritis of the hand.

OBJECTIVE: To describe the association between sex, smoking, physical activity, occupation, and previous digit fracture and hand osteoarthritis (OA). METHODS: Cross sectional study of 522 subjects from 101 Tasmanian families (348 women, 174 men). Hand OA was assessed by 2 observers using the OARSI atlas for joint space narrowing and osteophytes at distal interphalangeal (DIP) and carpometacarpal joints as well as a score for Heberden's nodes based on hand photography. A structured questionnaire collected information regarding physical activity, sport participation, occupation, and smoking history. RESULTS: Women had a higher prevalence of hand OA and the increase with age was significantly higher for women at all sites (all p < 0.05). Ever smoking was associated with less frequent (OR 0.59, 95% CI 0.38, 0.92) and less severe Heberden's nodes (beta -0.60, 95% CI -1.03, -0.17), but not radiological disease. Recall of occupation, physical activity, and sport participation between the ages of 20 and 40 years had no association with the prevalence or severity of hand OA, while self-reported digital fracture was significantly associated with more common (OR 2.42, 95% CI 1.22, 4.83) and severe DIP joint disease (beta +3.92, 95% CI +1.50, +6.36). No factors were associated with carpometacarpal disease. CONCLUSION: In this sample, women had a higher prevalence of hand OA at all sites as well as greater severity and a steeper age gradient (implying higher incidence rates). Smoking may decrease the risk of Heberden's nodes while having no effect on radiological hand OA, suggesting a differential effect possibly at the time of disease onset. With the exception of digital fracture, these data do not support a causal role for occupation or activity in earlier life with regard to hand OA.