Prevention and management of glucocorticoid-induced osteoporosis.
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Arthritis, Rheumatoid↗
Biomedical subjects
N E Lane
Publications and source records attributed to N E Lane.
Radiographic indices for osteoarthritis.
There are now validated radiographic indices that can be used by clinical investigators to determine the prevalence and severity of OA of the hand, hip, knee, apophyseal joints of the cervical and lumbar spine, and cervical disc degeneration. Clinical investigators should consult standardized atlases for radiographic index descriptions. The use of an atlas and training sessions improve the agreement between and within readers. The standard global grades developed by Kellgren and Lawrence have been used in epidemiologic studies to determine the prevalence of OA in specific joints. The evaluation of radiographic OA by individual radiographic features allows for the characterization of the variation in radiographic features often found in OA and in degenerative disc disease. Methods have been developed to maintain interrater and intrarater agreement in scoring radiographs. Radiographic indices of OA can now be reliably applied to clinical epidemiologic-based studies of OA.
Arthrography↗
Nonsteroidal antiinflammatory drugs: effects on normal and interleukin 1 treated human articular chondrocyte metabolism in vitro.
OBJECTIVE: To test the effects of nonsteroidal antiinflammatory drugs (NSAID), naproxen, ibuprofen and diclofenac, and salicylates on normal and interleukin 1 (IL-1) treated human articular chondrocyte metabolism in vitro. METHODS: Normal adult human articular chondrocytes were isolated and cultured as primary monolayers; the cells were treated with NSAID and salicylates at low and high plating density for assessing effects on proliferation and matrix synthesis and IL-1 modulated cell metabolism, respectively. RESULTS: Cell proliferation was inhibited by ibuprofen and high doses of salicylates. Glycosaminoglycan (GAG) synthesis was stimulated by ibuprofen at 10 micrograms/ml but was not changed by any other drugs at similarly low concentrations; at medium to high concentrations, only the salicylates inhibited GAG synthesis. Collagen synthesis was unaffected by any drug at the concentrations tested. IL-1 induced prostaglandin E2 release was completely inhibited by the NSAID and partially inhibited by the salicylates. IL-1 induced IL-6 release was inhibited by ibuprofen and the salicylates where as IL-1 induced APMA-activated collagenase was only inhibited by the salicylates. CONCLUSION: Normal human chondrocytes respond differentially to naproxen, ibuprofen, dicolfenac, and the salicylates; these observations suggest that each drug may exhibit unique attributes with respect to longterm efficacy on cartilage metabolism.
Cartilage, Articular↗
Exercise: a cause of osteoarthritis.
Regular exercise has become an international pastime, and physicians question if regular exercise will accelerate the development of osteoarthritis (OA). I review current literature about the effect of regular exercise on the risk of developing OA in normal and abnormal joints. With low impact activities, the risk of developing OA in normal joints is not increased. Individuals who participate in sports with abnormal or injured joints or at a highly competitive (elite) level appear to be at increased risk of developing OA. Longitudinal studies of young athletes after elite level performance or after joint injuries will allow us to substantiate these findings.
Exercise↗
The association of radiographic changes of osteoarthritis of the hand and hip in elderly women.
OBJECTIVE: To examine the association of radiographic features of hand and hip osteoarthritis (OA) in elderly women. METHODS: Hand and hip radiographs were read for changes of OA from a sample of 1422 women aged 65 and above who were participants in the Study of Osteoporotic Fractures. Definite hip OA required the presence of 2 or more of the following: moderate or large osteophytes, moderate or severe joint space narrowing, subchondral sclerosis, cysts, and femoral head deformity. Definite hand OA required moderate or large osteophytes at 2 or more of the following 6 sites: 2nd and 3rd distal and proximal interphalangeal joints and 1st interphalangeal and carpometacarpal joints. Data were analyzed using multiple logistic regression adjusting for age, weight at age 50, and current height. RESULTS: Overall, 147 (10.4%) women had radiographic changes of definite hip OA and 68 (4.8%) had severe hip OA; 56 had bilateral and 87 had unilateral disease. Definite hand OA was present in 732 (51.4%) women. Hand OA was significantly associated with definite hip OA [odds ratio (OR) = 3.25, 95% confidence intervals (CI) 2.19, 4.84], and severe hip OA (OR = 3.23, 95% CI 1.82, 5.73). Hand OA was significantly associated with bilateral hip OA (OR = 3.54, 95% CI 1.87, 6.73) as well as unilateral hip OA (OR = 3.06, 95% CI 1.84, 5.08). CONCLUSION: These data are consistent with the inclusion of radiographically defined hip OA in the construct of generalized OA, particularly in elderly women.
Aged↗
Running and the development of disability with age.
OBJECTIVE: To determine, by longitudinal study, whether regular vigorous running activity is associated with accelerated, unchanged, or postponed development of disability with increasing age. STUDY DESIGN: 8-year prospective, longitudinal study with yearly assessments. PARTICIPANTS: 451 members of a runners' club and 330 community controls who were initially 50 to 72 years old (also characterized as "ever-runners" [n = 534] and "never-runners" [n = 247], respectively). MEASUREMENTS: The dependent variable was disability as assessed by the Health Assessment Questionnaire and separately validated in these participant cohorts. Covariates included age, sex, body mass index, comorbid conditions, education level, smoking history, alcohol intake, mean blood pressure, initial disability level, family history of arthritis, and radiologic evidence of osteoarthritis of the knee in a subsample. RESULTS: Initially, the runners were leaner, reported joint symptoms less frequently, took fewer medications, had fewer medical problems, and had fewer instances of and less severe disability, suggesting either that the average previous 12 years of running had improved health or that self-selection bias was present. After 8 years of longitudinal study, the differences in initial disability levels (0.026 compared with 0.079; P < 0.001) had steadily increased to 0.071 for runners compared with 0.242 for controls (P < 0.001). The difference was consistent for men and women. The rate of development of disability was several times lower in the runners' club members than in community controls; this difference persisted after adjusting for age, sex, body mass, baseline disability, smoking history, history of arthritis, or other comorbid conditions (slopes of progression of disability for the years 1984 to 1992, after adjusting for covariates: men in the runners' club, 0.004 [SE, 0.002]; community controls, 0.012 [SE, 0.002]; women in the runners' club, 0.009 [SE, 0.005]; community controls, 0.027 [SE, 0.004]; P < 0.002 for both sets of comparisons). In addition to differences in disability, there were significant differences in mortality between the runners' club members (1.49%) and community controls (7.09%) (P < 0.001). These differences remained significant after adjusting for age, sex, body mass, comorbid conditions, education level, smoking history, alcohol intake, and mean blood pressure (P < 0.002, conditional risk ratio for community controls compared with the runners, 4.27; 95% CI, 1.78 to 10.26). CONCLUSIONS: Older persons who engage in vigorous running and other aerobic activities have lower mortality and slower development of disability than do members of the general population. This association is probably related to increased aerobic activity, strength, fitness, and increased organ reserve rather than to an effect of postponed osteoarthritis development.
Aging↗
Exercise and the musculoskeletal system.
1. Normal joints in individuals of all ages may tolerate prolonged and vigorous exercise without adverse consequences or accelerated development of OA. 2. Individuals who have underlying muscle weakness or imbalance, neurological abnormalities, anatomical variances, and who engage in significant amounts of exercise that stress the lower extremities, may accelerate the development of OA. 3. Individuals who have suffered injuries to supporting structures may also be susceptible to accelerated development of OA in weight-bearing joints, even without increased stress to the joint from exercise. 4. Certain individuals with established degenerative or inflammatory arthritis may benefit from supervised exercise programmes. 5. Still more information is needed so that physicians can identify subjects at risk for the development of OA, advise the millions of participants about the beneficial and deleterious effects of regular exercise and sports participation, and develop successful rehabilitation programmes for injured joints.
Exercise↗
Current and investigational approaches for reversing established osteoporosis.
Osteoporosis is a disease of elderly women marked by low bone mass and increased risk of fracture. Though its prevalence can be reduced by timely estrogen replacement at menopause, many persons present with fragility fractures long after much bone has been lost. Osteoporotic subjects have low bone mass and poor structure but few or no metabolic abnormalities, such as ongoing bone loss, for treatment to normalize. The problem is to increase their bone mass and improve their bone structure. Today's major therapeutic approaches are summarized in Table 2. Ironically, they aim at stopping bone loss. Although preventing the skeleton of an osteoporotic person from growing weaker by stopping bone loss is better than allowing the process to continue, raising her to a significantly higher level of bone mass would be a better aim. Existing agents that stop bone loss by reducing turnover also increase bone mass mildly by filling the remodeling space. The result is a rise in bone mass during the first year or two of treatment to a new steady state 2% to 5% higher than baseline that persists throughout treatment. Fluoride increases spinal bone mass markedly. It decreases vertebral, but not hip fractures, but is associated with side effects and a nonresponse rate that makes pursuing other therapies attractive. Agents that upregulate bone mass through regulatory means have been tested in preclinical and a few clinical trials. PGE2 has been thoroughly tested preclinically. By studying PGE2, the field has learned that marked bone mass increases in the estrogen-deplete osteopenic skeleton are possible. The lack of bone specificity for PGE2 will probably limit its use to that of preclinical demonstration agent but leave open the possibility that less potent members of the prostaglandin family with better bone specificity might have promise as osteoporosis treatments. PTH or one of its analogues shows good promise for osteoporosis treatment. The wide availability of cheap PTH or proprietary analogues with similar activity will do much to speed its development. It increases bone formation and cancellous bone mass markedly. If PTH increases bone mass consistently in either large animal or human trials while causing only mild transient cortical bone mass declines, it can be a successful osteoporosis treatment agent. Bone growth factors appear to have much untapped potential for furthering the understanding of local control of bone processes and possibly for treating osteoporosis. Another possibility is biphasic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
Estimating lumbar bone mineral density from routine radiographs of the lumbar spine.
To evaluate the information content of lateral lumbar films with respect to bone mineral content, we compared reading criteria with values obtained by quantitative computed tomography (CT) of L1 at baseline and after 5 years. The highest correlations with mineral content were found for the criteria "overall assessment of the vertebra", "vertebral bone density versus soft tissue", and "amount of trabeculations". These three reading criteria yielded higher correlations with CT scores in subjects with lower body mass index. Changes in mineral content over the 5-year period could not be read adequately, the average difference representing only a loss of about 10% in the study subjects. We conclude that a rough estimate of bone density can be obtained from lateral radiographs which, in the presence of eventual risk factors for osteoporosis, may serve as an additional indication to timely bone densitometry with methods which allow precise short-term follow-up measurements.
Aged↗
Exercise: a cause of osteoarthritis?
A common question posed to rheumatologists by both patients and physicians is 'What is the role of exercise in arthritis?' Practitioners and patients want to know if regular exercise is a risk factor for the later development of osteoarthritis. This article briefly reviews the epidemiology of osteoarthritis and exercise and risk factors associated with the development of osteoarthritis in athletes. It also reviews how musculoskeletal tissues respond to loading in normal and injured states. Finally, the topic of exercise for arthritic patients is reviewed, and recommendations are given.
Adaptation, Physiological↗
Reliability of new indices of radiographic osteoarthritis of the hand and hip and lumbar disc degeneration.
OBJECTIVE: To develop a method for assessing the presence and severity of radiographic features of osteoarthritis (OA) of the hip and hand, and thoracic and lumbar disc degeneration. METHODS: An atlas illustrating scoring of individual radiographic features and summary grades for individual joints was developed. Three readers evaluated 31 pelvic films, 27 hand films, and 25 lateral lumbar and thoracic spine films selected from a community based sample of healthy elderly women. Interrater agreement between the 3 readers, and test-retest agreement for one of the readers, were estimated by the intraclass correlation coefficient (ICC) and kappa statistic. RESULTS: Interrater agreement (ICC, unless otherwise noted) for individual radiographic features of the hip ranged from 0.66 for osteophytes to 0.80 for narrowing. For the 9 interphalangeal (IP) joints of the hand, agreement ranged from 0.42 (kappa) for sclerosis to 0.93 for narrowing, and for the lumbar spine from 0.55 (kappa) for sclerosis to 0.95 for narrowing. Interrater agreement for summary grades of radiographic findings was as follows: hip, 0.81; 5 distal interphalangeal joints (DIP), 0.89; 4 proximal interphalangeal joints (PIP), 0.82; and lumbar spine, 0.93. Intrarater agreement for summary grades was as follows: hips, 0.79; 5 DIP, 0.86; 4 PIP, 0.81; and lumbar spine, 0.90. CONCLUSION: We have developed reliable indices of the presence and severity of radiographic features of hip and hand OA and spinal disc degeneration for use in epidemiologic studies. The assessment includes grading of individual radiographic features, which allows for the independent variation in these features often found in OA and a summary grade of disease that is derived from the presence and severity of individual features.
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The relationship between spinal and peripheral osteoarthritis and bone density measurements.
OBJECTIVE: To determine the influence of osteoarthritis (OA) on bone density measurements and whether OA at one site is associated with OA at other sites. METHODS: Nonrandomized, cross sectional observational study; secondary analysis of a general population database. Sixty-four subjects derived from a longitudinal study of long distance runners and community controls had a complete peripheral radiographic evaluation for osteoarthritic changes in hands, knees, and lumbar spine. Forty-four of these were studied in 1984 with quantitative computed tomography (QCT) of L1, and 54 were studied in 1988 with 153-Gd dual photon absorptiometry (DPA) in the spine and total body. Thirty-four subjects had all measurements done. RESULTS: Total body and lumbar spine DPA were positively correlated with radiological scores of OA in the spine and knees, with coefficients ranging between 0.467 to 0.530 (p < 0.001 in all cases). This correlation was principally associated with spinal spurs and knee sclerosis. Results of stepwise multiple linear regression modeling for QCT included age, spine sclerosis, knee sclerosis and knee spurs as the main predictors of bone mineral density (BMD). For DPA measurements, spine spur score was a useful regressor for all the models. Altogether, the percentage of variance accounted for by individual radiological OA variables was 27.4% for lumbar QCT, 27.3% for lumbar BMD, 7.3% for total spine BMD, and 45.2% for total body BMD. OA scores at different sites were not correlated, although repeated assessment at the same site showed very close correlation. CONCLUSIONS: All methods used to determine BMD showed a highly significant positive correlation between lumbar and knee radiological OA and bone mineral content both in the spine and the total body. Thus, our results support the hypothesis that OA is negatively correlated with osteopenia. OA, as seen in this population, was not a generalized condition, but rather, was site specific.
Aged↗
The risk of osteoarthritis with running and aging: a 5-year longitudinal study.
Our purpose was to determine the 5-year longitudinal effects of running and aging on the development of radiographic and clinical osteoarthritis (OA) of the knees, hands and lumbar spine. Thirty-five running subjects and 38 controls, with a mean age of 63 years, were matched for age (+/- 2 years), years of education, and occupation; 33 matched pairs were constructed. All subjects underwent rheumatologic examination, completed questionnaires, and had radiographs taken of the hands, lateral lumbar spine, and knees in 1984 and in 1989. Five year radiographic results for both the runner and control groups showed OA progression for the knees, hands, and lumbar spine. In 1989, 10 (13%) of the 73 subjects fit American College of Rheumatology (ACR) criteria for clinical OA of the hand, and 9 subjects (12%) fit ACR criteria for OA of the knee. In summary, running did not accelerate the development of radiographic or clinical OA of the knees, but with aging, 13% of all subjects developed OA of the hands and 12% of all subjects developed OA of the knees.
Aged↗
Osteophytosis of the knee: association with changes in weight-bearing exercise.
Osteoarthritis has been held to result from wear and tear. We addressed this hypothesis by analysis of anteroposterior radiographs of the knees of 51 subjects with mean age of 60 years who regularly practiced weight-bearing exercise. Radiographs were assessed for longitudinal changes in spur formation over a two-year period. The results showed a negative association between changes in weight-bearing exercise and changes in the rate of spur development in both males and females. The findings suggest that increasing repetitive impulse loading in the form of regular painless weight-bearing activity does not promote osteophytosis (or perhaps degenerative disease) in knee joints.
Aged↗
Development of microcomputer-based mental acuity tests.
Recent disasters have focused attention on performance problems due to the use of alcohol and controlled substances in the workplace. Environmental stressors such as thermal extremes, mixed gases, noise, motion, and vibration also have adverse effects on human performance and operator efficiency. However, the lack of a standardized, sensitive, human performance assessment battery has probably delayed the systematic study of the deleterious effects of various toxic chemicals and drugs at home and in the workplace. The collective goal of the research reported here is the development of a menu of tests embedded in a coherent package of hardware and software that may be useful in repeated-measures studies of a broad range of agents that can degrade human performance. A menu of 40 tests from the Automated Performance Test System (APTS) is described, and the series of interlocking studies supporting its development is reviewed. The APTS tests, which run on several versions of laptop portables and desktop personal computers, have been shown to be stable, reliable, and factorially rich, and to have predictive validities with holistic measures of intelligence and simulator performances. In addition, sensitivity studies have been conducted in which performance changes due to stressors, agents, and treatments were demonstrated. We believe that tests like those described here have prospective use as an adjunct to urine testing for the screening for performance loss of individuals who are granted access to workplaces and stations that impact public safety.
Alcoholic Intoxication↗
Impact of running on lumbar bone density: a 5-year longitudinal study.
Our study was designed to examine associations of longterm physical impact (running) with changes in lumbar bone mineralization. Study subjects were a volunteer sample of 14 members of a running club now aged 55 to 77 years and 14 matched controls undergoing computerized scans of the first lumbar vertebra both at baseline and after 5 years. Separate analyses included data from 23 runners available over the entire 5-year period. A decrease in bone mineral density (BMD) over time was statistically significant in both runners and controls. Among runners bone loss was most pronounced in those decreasing their running habits substantially. At the 5-year mark, runners maintained greater BMD. A highly significant correlation was found between change in lumbar BMD and average time spent running (min/week) over the 5-year period. Furthermore, changes in BMD were positively correlated with changes in run min/week. We conclude that regular running appears to reduce age related bone loss both in women and men over 50 years of age. However, substantial decreases in physical weight bearing activity are associated with important bone loss in the lumbar spine.
Aged↗
Inhibition of interleukin 1 induced chondrocyte protease activity by a corticosteroid and a nonsteroidal antiinflammatory drug.
We report that administration of the corticosteroid, methylprednisolone (PRED) inhibited interleukin 1 (IL-1) induction of chondrocyte caseinolytic activity (25-55%) and collagenolytic activity (15-24%). The nonsteroidal antiinflammatory drug (NSAID), naproxen (NAP) had no effect on either enzyme activity over a therapeutic range (7-30 micrograms/ml) but at 120 micrograms/ml inhibited IL-1 induced caseinolytic and collagenolytic activity by 17 and 19%, respectively. However, PRED (2 micrograms/ml) in combination with NAP (30 micrograms/ml) significantly increased the inhibition of caseinolytic activity (p less than 0.001) compared to that observed with PRED (2 micrograms/ml) alone. The suppression of IL-1 induced collagenolytic activity noted with PRED in combination with NAP did not exceed that observed with PRED alone.
Adrenal Cortex Hormones↗