Consensus recommendations for the assessment and treatment of rheumatoid arthritis.
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Antirheumatic Agents↗
Biomedical subjects
N E Lane
Publications and source records attributed to N E Lane.
Starting a disease modifying antirheumatic drug or a biologic agent in rheumatoid arthritis: standards of practice for RA treatment.
Our aim was to investigate the practices and standards by which disease modifying antirheumatic drugs (DMARD) and biologics are and have been prescribed. We reviewed the literature and examined data from patients with rheumatoid arthritis (RA) participating in a national cohort: the National Data Bank for Rheumatic Diseases (NDB). Four pathways for DMARD prescription were identified: (1) A time-based pyramidal approach (the RA pyramid); (2) a severity-based pyramid in which the most effective treatment is given to those with more active disease; (3) a cost-based pathway in which the primary goal is cost containment--this pathway intertwines with the severity-based pathway; and (4) a patient preference pathway where treatment is geared to patient needs and wishes regardless of severity. Data show that the time-based and severity-based pathways are not generally used in contemporary expert practice, and that patients with all degrees of severity and disease duration are receiving DMARD and biologic treatment. With the abandonment of the pyramid and the development of effective therapy, rheumatic disease care has swung away from the imperative of time and severity-based treatment to the imperative of care based on patient preference. It is the standard of practice to treat patients with mild and early disease with aggressive therapy, with the goal of limiting subsequent damage and retarding progression, and with the realistic purpose of relieving symptoms. The standard may at times be in conflict with the goals of insurers, but there is no legitimate medical reason for such limitations.
Antirheumatic Agents↗
Osteoarthritis: new insights. Part 1: the disease and its risk factors.
Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weight-bearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability.
Age Distribution↗
Osteoarthritis: current concepts in diagnosis and management.
Most patients with osteoarthritis seek medical attention because of pain. The safest initial approach is to use a simple oral analgesic such as acetaminophen (perhaps in conjunction with topical therapy). If pain relief is inadequate, oral nonsteroidal anti-inflammatory drugs or intra-articular injections of hyaluronic acid-like products should be considered. Intra-articular corticosteroid injections may provide short-term pain relief in disease flares. Alleviation of pain does not alter the underlying disease. Attention must also be given to nonpharmacologic measures such as patient education, weight loss and exercise. Relief of pain and restoration of function can be achieved in some patients with early osteoarthritis, particularly if an integrated approach is used. Patients with advanced disease may eventually require surgery, which generally provides excellent results.
Algorithms↗
Association of mild acetabular dysplasia with an increased risk of incident hip osteoarthritis in elderly white women: the study of osteoporotic fractures.
OBJECTIVE: To determine if acetabular dysplasia increases the risk of incident hip osteoarthritis (OA) among elderly white women. METHODS: Baseline and followup anteroposterior pelvic radiographs were obtained a mean of 8 years apart, and read for individual radiographic features (IRFs) of hip OA; summary grades (0-4) were then assigned based on the IRFs present. Acetabular dysplasia was defined by the results of measurements of the acetabular depth (<9 mm) or the center-edge angle (<30 degrees). Logistic regression analyses were performed to determine the association between acetabular dysplasia and incident hip OA, and all analyses were adjusted for age, current weight, body mass index, affected side, and investigational site. RESULTS: The odds ratios for the association of abnormal center-edge angle and acetabular dysplasia with incident hip OA were 3.3 (95% confidence interval 1.1-10.1) and 2.8 (95% confidence interval 1.0-7.9), respectively. CONCLUSION: Acetabular dysplasia, defined by a decrease in the center-edge angle, is associated with a modestly increased risk of incident hip OA in elderly white women.
Acetabulum↗
Tibial plateau fracture as a measure of early estrogen-dependent bone fragility in rats.
The goals of this study were to develop a protocol to induce a compressive fracture at the tibial plateau of the rat knee in vitro and to determine if the biomechanical parameters provided a sensitive assessment of the early skeletal changes induced by estrogen deficiency. Sixty-one rats underwent an ovariectomy (n = 36) or sham operation (n = 25) and were maintained for 50 days after the procedure. Just before death, the proximal tibia of each animal was scanned with high-resolution x-ray tomography. From the three-dimensional images, the mean trabecular bone volume, thickness, and separation and the number of trabeculae were calculated. The knees were then harvested and mounted into a servohydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture. The fracture load of the ovariectomized rats was 24% less than that of the rats that had the sham operation. Similarly, the structural stiffness of the ovariectomized knees was decreased by 22%. Both of these differences were statistically significant (p < 0.01) and were explained by differences in trabecular bone volume (r = 0.56, p < 0.0001 and r = 0.42, p < 0.005, respectively). The other measures of trabecular bone structure were correlated with the volume and did not improve the prediction by the biomechanical parameters. These data demonstrate that biomechanical testing of the tibial plateau in rats can quantify the structural consequences of estrogen deficiency at an early time point before they become apparent at other bone sites, such as the lumbar spine.
Animals↗
Short-term increases in bone turnover markers predict parathyroid hormone-induced spinal bone mineral density gains in postmenopausal women with glucocorticoid-induced osteoporosis.
The purpose of this study was to test the ability of early changes in markers of bone turnover to predict subsequent changes in bone mineral density (BMD) induced by parathyroid hormone fragment, PTH (1-34), in postmenopausal osteoporotic women treated with estrogen and glucocorticoids. Forty-nine postmenopausal women with chronic, inflammatory diseases and BMD T-scores < or = -2.5 at the lumbar spine or femoral neck who were concurrently treated with estrogen > or = 1 year and prednisone 5-20 mg/day for > or = 1 year participated. Subjects were randomized to treatment with human PTH (1-34) 400 IU/day or to a control group for 1 year and followed for an additional year. Serum and urine were collected at baseline and 1, 3, 6, 9, 12, 18 and 24 months for measurement of bone alkaline phosphatase (BAP), osteocalcin (OC) and deoxypyridinoline (DPD). We constructed an Uncoupling Index (UI) from all three markers (UI = [ZBAP + Zoc]/2 -ZDPD, where the Z-score for each marker in each subject was calculated from the mean and standard deviation of the study population at baseline). BMD of the lumbar spine and hip was measured at baseline and every 6 months thereafter by dual-energy X-ray absorptiometry (DXA) and annually by quantitative computed tomography (QCT; spine only). BMD of the spine, but not hip (total, femoral neck or trochanter), and levels of all three markers increased significantly as a result of PTH treatment (p<0.01 compared with controls). The resorption response lagged behind that of formation as evidenced by a significant increase (p < 0.05) in the UI for the first 9 months of treatment. The UI values and changes from baseline to 1, 3 and 6 months in BAP, OC and DPD were correlated with the 12- and 24-month changes in spine BMD measured both with QCT and with DXA (Spearman's rank coefficients <0.76; p<0.05). Most PTH-treated subjects could be identified as biochemical responders by least significant change analysis. Following 1 month of therapy, BAP and OC identified 65% and 81% as responders, respectively. The responder rates were 79%, 79% and 75% for BAP, OC and DPD, respectively by 6 months. Responders exhibited a high level of diagnostic accuracy for predicting a gain in BMD (areas under the receiver operating characteristic curves exceeding 0.79 for QCT and 0.70 for DXA), but not the magnitude of the gain. These data suggest that serial bone marker measurements may be useful in identifying skeletal responders to an anabolic therapy, such as PTH, in estrogen-replete postmenopausal women with glucocorticoid-induced osteoporosis.
Aged↗
Steroid-induced osteoporosis in systemic lupus erythematosus.
The patient with SLE is at considerable risk of osteoporosis, because of the inflammatory disease itself, its consequences, and its treatments. Because of their extensive use, glucocorticoids are thought to be the most frequent cause of drug-related osteoporosis and may be responsible for much of the bone loss in lupus. This article focuses on the mechanisms of steroid-induced osteoporosis in SLE and outlines strategies for prevention and treatment.
Calcium↗
Compliance with national recommendations for tuberculosis screening and immunization of healthcare workers in a children's hospital.
Physicians and clinical employees at a children's hospital were surveyed to compare their tuberculosis (TB) screening and immunization statuses. Failure to offer screening and immunization services to non-employee physicians was associated with lower rates of reported immunity to several vaccine-preventable diseases and with markedly lower rates of TB screening.
Guideline Adherence↗
Three-dimensional morphometry of the L6 vertebra in the ovariectomized rat model of osteoporosis: biomechanical implications.
This article summarizes the results of a three-dimensional study of changes in the morphology of the L6 rat vertebra at 120 days after ovariectomy (OVX), with estrogen replacement therapy used as a positive control. Synchrotron radiation microtomography was used to quantify the structural parameters defining trabecular bone architecture, while finite-element methods were used to explore the relationships between these parameters and the compressive elastic behavior of the vertebrae. There was a 22% decrease in trabecular bone volume (TBV) and a 19% decline in mean trabecular thickness (Tb.Th) with OVX. This was accompanied by a 150% increase in trabecular connectivity, a result of the perforation of trabecular plates. Finite-element analysis of the trabecular bone removed from the cortical shell showed a 37% decline in the Young's modulus in compression after OVX with no appreciable change in the estrogen-treated group. The intact vertebrae (containing its trabecular bone) exhibited a 15% decrease in modulus with OVX, but this decline lacked statistical significance. OVX-induced changes in the trabecular architecture were different from those that have been observed in the proximal tibia. This difference was a consequence of the much more platelike structure of the trabecular bone in the vertebra.
Animals↗
Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial.
Glucocorticoid-induced osteoporosis is the most common secondary cause of osteoporosis. In this 24-month study, we report changes in bone turnover and bone mass after 12 months of daily injections of human parathyroid hormone 1-34 [hPTH(1-34)] and 12 months off treatment in postmenopausal women (mean age, 63 years) with osteoporosis treated with glucocorticoid and hormone replacement therapy. Response to the treatment was assessed with bone mineral density (BMD) measurements of the lumbar spine by quantitative computed tomography (QCT); BMD measurements of the lumbar spine, hip, and forearm by dual-energy X-ray absorptiometry (DXA); and biochemical markers of bone turnover. The mean (+/-SEM) change in BMD of the lumbar spine by QCT and DXA in the PTH group at 24 months was 45.9+/-6.4% and 12.6+/-2.2% (p < 0.001). The change in total hip and femoral neck BMD was not significant at 12 months but increased to 4.7+/-0.9% (p < 0.01) and 5.2+/-1.3% at 24 months, respectively, as compared with a relatively small change of 1.3+/-0.9% and 2.6+/-1.7% in the estrogen-only group. The mean percent differences in BMD of the lumbar spine by QCT and DXA between the groups at 24 months were 43.1% and 11.9%, respectively (p < 0.001). The mean percent differences over the estrogen-only group in hip BMD were 3.4% for total hip (p < 0.01) and 2.6% for femoral neck at 24 months. Biochemical markers of bone turnover increased to more than 150% during the first 6 months of therapy, remained elevated throughout the 12-month treatment period, and returned to baseline values within 6 months of discontinuing the PTH treatment. These results suggest that PTH dramatically increases bone mass in the lumbar spine and hip in postmenopausal women with glucocorticoid-induced osteoporosis who are taking hormone replacement therapy. However, the maximum effect of this anabolic agent on bone mass at the hip after 12 months of treatment requires at least 6-12 months after the PTH treatment is discontinued.
Absorptiometry, Photon↗
Getting control of osteoarthritis pain. An update on treatment options.
Osteoarthritis consists of a heterogeneous group of disorders that result in articular cartilage degeneration and is diagnosed on the basis of clinical findings. Pathogenesis involves an imbalance between the synthetic and degradative processes that occur in joints. Current interest in the role of cytokines and metalloproteinases may lead to improved treatment of osteoarthritis. For now, management consists of combinations of pharmacologic and nonpharmacologic therapies. A general pharmacologic approach is to begin with acetaminophen and add a low-dose NSAID, nonacetylated salicylate, selective COX-2 inhibitor, or topical capsaicin cream if needed. If pain persists, full-dose NSAID therapy, with the addition of a protective agent in patients at risk for gastrointestinal bleeding, or full-dose COX-2 inhibitor therapy may be tried. Joint injections, irrigation, or arthroscopy may be beneficial in some cases. In patients who continue to have pain and limited function despite these measures, surgical intervention should be considered.
Humans↗
Serum vitamin D levels and incident changes of radiographic hip osteoarthritis: a longitudinal study. Study of Osteoporotic Fractures Research Group.
OBJECTIVE: The purpose of this study was to determine the relationship of serum levels of 25-vitamin D and 1,25-vitamin D to incident changes of radiographic hip osteoarthritis (OA) among elderly white women. METHODS: Baseline and followup hip radiographs of 237 subjects were obtained an average of 8 years apart. Hips were scored for individual radiographic features (IRF) and assigned a summary grade based on the number and type of IRF present. Serum 25- and 1,25-vitamin D levels from baseline samples were analyzed by radioimmunoassay. Logistic and linear regression were used to examine the association of 25- and 1,25-vitamin D levels with radiographic changes, adjusting for age, health status, physical activity, weight, vitamin D supplement use, and calcaneal bone mineral density. RESULTS: The risk of incident hip OA defined as the development of definite joint space narrowing was increased for subjects who were in the middle (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.06, 9.68) and lowest (OR 3.34, 95% CI 1.13, 9.86) tertiles for 25-vitamin D compared with subjects in the highest tertile. Vitamin D levels were not associated with incident hip OA defined as the development of definite osteophytes or new disease according to the summary grade. No association between serum 1,25-vitamin D and changes in radiographic hip OA was found. CONCLUSION: Low serum levels of 25-vitamin D may be associated with incident changes of radiographic hip OA characterized by joint space narrowing.
Aged↗
Osteoarthritis and risk of falls, rates of bone loss, and osteoporotic fractures. Study of Osteoporotic Fractures Research Group.
OBJECTIVE: To examine the association between osteoarthritis (OA), as defined by radiographic evidence and self report, and osteoporotic fractures, falls, and bone loss in a cohort of elderly white women. METHODS: A cohort of 5,552 elderly women from the Study of Osteoporotic Fractures was followed up prospectively for a mean of 7.4 years. Self-reported, physician-diagnosed OA was recorded at interview, and radiologic OA of the hip and hand were defined from pelvis and hand radiographs obtained at baseline by validated techniques. Prevalent and incident vertebral fractures were detected by vertebral morphometry, and data on incident fractures and falls were collected by postcard surveys; fractures were confirmed by radiography. Bone mineral density (BMD) was measured on 2 occasions at the hip, lumbar spine, and calcaneus, and rates of bone loss were calculated. RESULTS: Women with radiographic hip OA had a reduced risk of recurrent falls in the first year (relative risk [RR] 0.7, 95% confidence interval [95% CI] 0.5-0.95). However, those with self-reported OA had an increased risk of falls (RR 1.4, 95% CI 1.2-1.5). Radiographic hip OA was associated with reduced bone loss in the femoral neck compared with controls (mean +/- SD -0.29+/-0.09%/year versus -0.51+/-0.03%/year; P = 0.018). However, radiographic hip OA showed nonsignificant trends toward increased bone loss at the calcaneus and lumbar spine. There was no significant association between self-reported OA or radiographic hand OA with bone loss. No definition of OA was associated with incident nonvertebral fracture, hip fracture, or vertebral fracture. CONCLUSION: Despite having increased BMD compared with controls, subjects with OA did not have a significantly reduced risk of osteoporotic fracture, although there was a trend toward a reduced risk of femoral neck fractures in subjects with severe radiographic OA. The failure of the observed increase in BMD to translate into a reduced fracture risk may be due, in part, to the number and type of falls sustained by subjects with OA. Patients with OA should not be considered to be at a lower risk of fracture than the general population. Physicians should be aware that a high BMD in patients with OA may be falsely reassuring.
Accidental Falls↗
Trabecular bone architecture in the distal radius using magnetic resonance imaging in subjects with fractures of the proximal femur. Magnetic Resonance Science Center and Osteoporosis and Arthritis Research Group.
To determine whether magnetic resonance (MR)-derived measures of trabecular bone architecture in the distal radius are predictive for prevalent hip fractures, 20 subjects with hip fractures and 19 age-matched postmenopausal controls were studied. Bone mineral density (BMD) measures at the hip (dual-energy X-ray absorptiometry, DXA) and the distal radius (peripheral quantitative computed tomography, pQCT) were also obtained. We compared the MR-based structural measures derived in the radius with those in the calcaneus of the same patients. In the radius, images were acquired at an in-plane resolution of 156 microm and a slice thickness of 0.5 mm. Stereologic measures such as the apparent trabecular thickness (app. Tb.Th), fractional trabecular bone volume (app. BV/TV), trabecular spacing (app. Tb.Sp) and trabecular number (app. Tb.N) were derived from the images. Measures of app. Tb.Sp and app. Tb.N in the distal radius showed significant (p<0.05) differences between the two groups, as did hip BMD measures. However, radial trabecular BMD measures showed only a marginal difference (p = 0.05). Receiver operating curve analysis was used to determine the diagnostic efficacy of BMD, structural measures and a combination of the two. The area under the curve (AUC) for total hip BMD was 0.73, and for radial trabecular BMD was 0.69. AUC for most of the measures of trabecular bone structure at the distal radius was lower than for hip BMD measures; however, AUC for app. Tb.N at the radius was 0.69, comparable to trabecular BMD using pQCT. The AUC for combined BMD (hip) and structure measures was higher (0.87) when radius and calcaneus structure was included. Measures of trabecular architecture derived from MR images combined with BMD measures improve the discrimination between subjects with hip fractures and normal age-matched controls.
Aged↗
Prevention of glucocorticoid-induced osteoporosis: provider practice at an urban county hospital.
PURPOSE: We sought to determine the frequency and types of prophylaxis for osteoporosis that were prescribed to outpatients who were receiving chronic glucocorticoid treatment and to identify the patient and provider characteristics that were associated with the use of prophylaxis. SUBJECTS AND METHODS: We identified 215 adult outpatients at San Francisco General Hospital who had received a prescription for prednisone (or its equivalent) at a daily dose of at least 5 mg for at least 1 month. Patient demographic characteristics, the diagnosis for which glucocorticoids were prescribed, comorbid illnesses, and medications were determined by chart review. Characteristics of the patients who were prescribed prophylaxis were compared with those of patients who were not prescribed prophylaxis. RESULTS: Prophylaxis for glucocorticoid-induced osteoporosis was prescribed to 58% of patients. Patients prescribed prophylaxis were older (mean [+/-SD] age of 50.0 +/- 13.9 versus 44.5 +/- 13.6 years, P = 0.004), more likely to be female (69% versus 40%, P <0.0001), postmenopausal if female (84% versus 56%, P = 0.002), have more comorbid illnesses (63% versus 29%, P = 0.001), and take multiple medications (66% versus 45%, P = 0.002). Patients attending the rheumatology clinic were 1.6 times more likely to receive prophylaxis than those attending other clinics (P <0.0001). The strongest predictor of prophylaxis was postmenopausal state. In premenopausal women, the independent predictors of prophylaxis were being treated in the rheumatology clinic and the presence of comorbid illnesses, whereas comorbid illnesses was the only independent predictor of prophylaxis in men. CONCLUSIONS: Educational efforts should be directed toward increasing awareness of the importance of glucocorticoid-induced osteoporosis and its prevention.
Adult↗
Exercise and osteoarthritis.
The relation of exercise to osteoarthritis is one of great interest and importance. In this paper, we review two recent studies. One reported that older individuals with normal knee and hip joints who jog for recreational activities do not have an increased risk for the development of osteoarthritis in weight-bearing joints. However, in another case-control study of women with hip osteoarthritis, the risk of hip osteoarthritis increased twofold with high levels of participation in recreational activities before the age of 50 years and fourfold for women with high levels of sporting activities and occupational physical loads. Therefore, participation in certain types of sporting activities and occupations that increase loading to the hip joint before the age of 50 years may be associated with an increased risk of hip osteoarthritis. However, recreational jogging in individuals 60 or more years of age with normal knee and hip joints does not increase the risk for the development of osteoarthritis. These studies add to our knowledge base regarding lifetime and current risk factors for the development of knee and hip osteoarthritis from exercise.
Exercise↗
Early estrogen replacement therapy reverses the rapid loss of trabecular bone volume and prevents further deterioration of connectivity in the rat.
To evaluate the ability of estrogen replacement therapy (ERT) to prevent changes in trabecular bone volume (BV/TV) and connectivity beginning either at ovariectomy (OVX) or 5-13 days after OVX in adult female rats, the right proximal tibial was examined by three-dimensional X-ray tomographic microscopy (XTM) in vivo. Animals had XTM scans of the right tibia and then were randomized into six groups (n = 9). Groups 2-6 had bilateral (OVX), while group 1 was sham-ovariectomized (OVXd) on day 0. Animals were treated with vehicle (groups 1 and 2) or 17beta-estradiol therapy (ERT) at 10 microg/kg three times per week starting at days 0, 5, 8, and 13 post-OVX (groups 3, 4, 5, and 6), until day 50 when they were rescanned by XTM and sacrificed. Trabecular bone structural variables were calculated from XTM data (BV/TVx and beta1/BV/TVx) and standard histomorphometry. Trabecular bone volume (BV/TVx) and the trabecular connections per cubic millimeter of trabecular bone (beta1/BV/TVx) were maintained in both sham-OVXd animals and OVX animals given ERT from the time of OVX. However, OVX + vehicle-treated animals lost 54% BV/TVx and 46% beta1/BV/TVx (p < 0. 01 from day 0). BV/TVx and beta1/BV/TVx decreased rapidly post-OVX to -22% and -25% at day 13 (p < 0.01 from day 0). ERT initiated at day 5, 8, and 13 post-OVX restored BV/TVx to baseline values at day 50 by modestly increasing trabecular plate thickness; however, beta1/BV/TVx was reduced in all OVX groups when compared with their baseline values. ERT also caused a significant reduction in bone turnover compared with OVX + vehicle; however, resorption was suppressed more than formation. These results demonstrate that ERT can restore the lost trabecular bone, but not trabecular connectivity, that occurs soon after OVX by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which prompt intervention with estrogen and other antiresorptive agents can restore bone mass that has been lost from the increase in remodeling space, and thereby reduce the risk of osteoporotic fractures in postmenopausal women.
Animals↗