PubMed Health⌕ Search

Biomedical subjects

N E Lane

Publications and source records attributed to N E Lane.

At least 19 recordsLinked to original sources
PubMed2003

Basic fibroblast growth factor forms new trabeculae that physically connect with pre-existing trabeculae, and this new bone is maintained with an anti-resorptive agent and enhanced with an anabolic agent in an osteopenic rat model.

Osteoporosis is a disease of excess bone fragility that results from both the loss of bone mass and trabecular bone microarchitecture, thereby creating a very fragile skeleton. The purpose of this study was to determine whether treatment of ovariectomized (OVX) osteopenic rats with basic fibroblast growth factor (bFGF) would stimulate the production of new trabeculae, and whether the newly formed trabeculae would make physical connections with the pre-existing trabeculae after prolonged estrogen deficiency. Six-month-old Sprague Dawley rats were OVXed or sham-operated and were left untreated until day 60 post-OVX. A high resolution microscopic scan (XTM) of the right proximal tibia was performed on groups 1 and 2 on day 1 post-OVX, and was repeated in all animals on day 60 post-OVX. At day 60 groups 1 and 2 were treated with vehicle and groups 3 to 6 were injected with bFGF 200 microg/kg/d intravenously for 15 days. At day 82, all animals obtained another in vivo XTM scan of the right tibia; then group 4 were treated with 17B estradiol 10 microg/kg/3x a week, group 5 were treated with hPTH (1-34) at 80 microg/kg/d for 35 days, group 6 were sacrificed, and groups 1 and 2 were treated with vehicle injections for 35 days. At day 110, all remaining animals were sacrificed, and repeat ex vivo XTM scans of the right proximal tibia were performed. Trabecular bone structural variables-including trabecular bone volume, connectivity, number, and thickness-were obtained from all XTM scans. Biochemical markers of bone turnover were also obtained 24 hours before each XTM scan (osteocalcin and deoxypyridinoline), and analyzed by ELISA. Animals OVXed and treated with vehicle had decreased trabecular bone volume, connectivity and number compared to sham-operated animals at both day 60 and day 110. Animals treated with bFGF from day 60-75 post-OVX had evidence of new trabeculae that physically connected with pre-existing trabeculae and also of increased trabecular bone volume seven days after the injections were discontinued. Biochemical markers of bone formation had a small and insignificant increase over baseline levels during the bFGF injections. Bone resorption markers were significantly reduced during the injection period, but returned to baseline levels after the injections were stopped. In addition, we also demonstrated that these newly formed trabecular connections could be maintained or added to with either estrogen or hPTH (1-34) treatments. Thirty-five days after ending the bFGF treatment, trabecular bone volume and connectivity was 25-80% higher in the estrogen and hPTH (1-34) treated animals compared to the untreated animals ( p<0.01). These results support continued development of bFGF as a potential treatment for severely osteoporotic individuals.

Animals↗
PubMed2003

Daily treatment with parathyroid hormone is associated with an increase in vertebral cross-sectional area in postmenopausal women with glucocorticoid-induced osteoporosis.

Daily treatment with hPTH (1-34) is associated with a significant increase in bone formation which results in large gains in lumbar spine bone mass. However, bone formation is known to occur on trabecular, endocortical and periosteal surfaces. The purpose of this study was to determine whether daily treatment with hPTH (1-34) for 1 year was associated with a change in vertebral cross-sectional area, or vertebral size, as measured by serial quantitative computed tomography scans. Fifty-one postmenopausal women treated chronically with both glucocorticoids and hormone replacement therapy (HRT) were randomized to either daily hPTH (1-34) for 1 year and HRT or to a control group treated with only HRT. Measurements of bone density of the spine were obtained every 6 months by dual-energy X-ray absorptiometry (DXA) and annually by QCT of the L1 and L2 vertebrae. Vertebral cross-sectional area (VCSA) was obtained from the QCT scans. In addition, we estimated the vertebral compressive strength (VSFOM, g(2)/cm(4) = trabecular BMD(2) x VCSA). After 1 year of hPTH (1-34) treatment, VCSA increased 4.8% (p < 0.001), and 1 year after treatment was discontinued VCSA was still 2.6% higher than the baseline value (p < 0.05). The control group had no change in VCSA. In addition, estimated vertebral compressive strength increased more than 200% over baseline levels in the hPTH (1-34) treatment group and no change was observed in the control group. In summary, daily treatment with hPTH (1-34) for 1 year increased vertebral size as measured by VCSA and this increase was maintained after hPTH (1-34) was discontinued. Since vertebral fracture risk is related to both bone size and bone mass, we cautiously speculate that the increase in vertebral size associated with hPTH (1-34) treatment is at least partially responsible for increased vertebral bone strength and reduction of fracture risk associated with this therapy in postmenopausal osteoporosis.

Absorptiometry, Photon↗
PubMed2002

Quantitative computed tomography of the lumbar spine, not dual x-ray absorptiometry, is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy.

OBJECTIVE: To determine which measurement of bone mineral density (BMD) predicts vertebral fractures in a cohort of postmenopausal women with glucocorticoid-induced osteoporosis. METHODS: We recruited 114 subjects into the study. All had osteopenia of the lumbar spine or hip, as demonstrated by dual x-ray absorptiometry (DXA), and were receiving long-term glucocorticoids and hormone replacement therapy (HRT). Measurements of BMD by DXA of the lumbar spine, hip (and subregions), and forearm (and subregions), quantitative computed tomography (QCT) of the spine and hip (n = 59), and radiographs of the thoracolumbar spine were performed on all subjects to assess prevalent vertebral fractures. Vertebral fracture prevalence, as determined by morphometry, required a >or=20% (or >or=4-mm) loss of vertebral body height. Demographic information was obtained by questionnaire. Multiple regression and classification and regression trees (CART) analyses were used to assess predictors of vertebral fracture. RESULTS: Twenty-six percent of the study subjects had prevalent fractures. BMD of the lumbar spine, total hip and hip subregions, as measured by QCT, but only the lumbar spine and total hip, as measured by DXA, were significantly associated with prevalent vertebral fractures. However, only lumbar spine BMD as measured by QCT was a significant predictor of vertebral fractures. CART analysis showed that a BMD value <0.065 gm/cm(3) was associated with a 7-fold higher risk of fracture than a BMD value >or=0.065 gm/cm(3). CONCLUSION: In postmenopausal women with osteoporosis induced by long-term glucocorticoid treatment who are also receiving HRT, BMD of the lumbar spine as measured by QCT, but not DXA, is an independent predictor of vertebral fractures.

Absorptiometry, Photon↗
PubMed2002

The effects of synthetic conjugated estrogens, a (cenestin) on trabecular bone structure and strength in the ovariectomized rat model.

This study evaluated the effect of Cenestin, a synthetic conjugated estrogens product, on the maintenance of trabecular bone microarchitecture, bone strength, and of bone turnover in the ovariectomized (ovx) rat model. Two doses of Cenestin were chosen in an attempt to approximate the equivalent human oral doses of 0.3 mg and 0.625 mg. Forty-nine 6-month-old retired female breeder Sprague-Dawley rats were randomly assigned to one of four groups: (1) sham-operated + vehicle; (2) ovx + vehicle; (3) ovx + day 1 post-ovariectomy Cenestin (8.12 mg/kg); (4) ovx + day 1 post-ovariectomy Cenestin (16.24 mg/kg) for 8 weeks. Trabecular structure of the right proximal tibia of each rat was imaged noninvasively by microCT. A compression test to induce a tibial plateau fracture was performed to determine the mechanical properties of the proximal tibia. Urine was collected on days 0, 14, 28, 42 and 56 and serum on days 0, 28 and 56 to assess biochemical markers of bone turnover including deoxypyridinoline crosslinks and osteocalcin. Both biochemical markers of bone turnover were analyzed by ELISA. Trabecular bone mass, structure, and connectivity density in the Cenestin-treated groups did not differ statistically ( p>0.05) from those of the sham-operated + vehicle-treated rats, but all were significantly higher ( p<0.05) than in the ovx + vehicle-treated rats. Structure Model Index, a measure of trabecular plate morphometry, in Cenestin-treated rats maintained a more equal mix of plate- and rod-like structures similar to the sham group, whereas the ovx group had predominantly rod-like trabeculae. Fracture load in the Cenestin (16.24 mg/kg) treated group was 31% ( p<0.01) higher than in the sham + vehicle-treated group and 61% ( p<0.05) higher than in the ovx + vehicle-treated group. Both the sham-operated + vehicle-treated and Cenestin-treated groups showed significantly lower urinary deoxypyridinoline crosslink excretion at all timepoints and serum osteocalcin at day 56 compared with the ovx + vehicle-treated group. In summary, Cenestin maintained trabecular bone microarchitecture and strength in an ovariectomized rat model of estrogen deficiency.

Animals↗
PubMed2002

Osteoporosis in the rheumatic disease patient.

Rheumatic disease patients often have both systemic and localized inflammatory processes. The result of this inflammation is tissue destruction and this translates into bone loss. Recent studies have highlighted the importance of systemic factors that either directly or indirectly activate receptor activator of nuclear factor-kappaB ligand (RANKL) dependent osteoclast activation and induce bone loss. In this article we will review the pathogenesis of inflammatory bone loss and explore the possible interventions to prevent it.

Animals↗
PubMed2001

Bone loss. Therapeutic approaches for preventing bone loss in inflammatory arthritis.

Inflammatory arthritides are commonly characterized by localized and generalized bone loss. Localized bone loss in the form of joint erosions and periarticular osteopenia is a hallmark of rheumatoid arthritis, the prototype of inflammatory arthritis. Recent studies have highlighted the importance of receptor activator of nuclear factor-kappa B ligand (RANKL)-dependent osteoclast activation by inflammatory cells and subsequent bone loss. In this article, we review the pathogenesis of inflammatory bone loss and explore the possible therapeutic interventions to prevent it.

Arthritis, Rheumatoid↗
PubMed2001

Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial.

OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

Adult↗
PubMed2001

The temporal changes of trabecular architecture in ovariectomized rats assessed by MicroCT.

To study the short- and long-term effects of estrogen deficiency on trabecular bone, three-dimensional measurements of proximal tibiae of ovariectomized rats were performed by micro-computed tomography (MicroCT). New three-dimensional (3D) techniques were employed to characterize the trabecular architecture from 0 to 110 days post-ovariectomy (OVX). These new methods no longer assume a plate or rod model of bone, but calculate trabecular thickness, separation, and number and their distribution by placing maximal spheres into the 3D representation of the structure. The model type of bone was quantified with the Structure Model Index (SMI). Utilizing these methods we found a rapid loss of trabecular bone in the first week after OVX. After the first week bone mass declined further, although the rate of loss was lower. In addition there was a complete change in model type from plate-like to rod-like within 7 days post-OVX, and then a very constant SMI after 12 days. After an initial thinning of trabecular structure, further bone loss seems to occur through removal of trabeculae, while the trabecular plate thickness remains constant. The heterogeneity of the network could be quantified by intra-individual standard deviation of local separations, which showed a stair-like progression, with a plateau between 12 and 60 days post-OVX. This study provides new insights into ovariectomy-related changes in cancellous bone structure evaluated by 3D MicroCT. In addition, these data suggest that the rapid change of model from plate-like to rod-like post-OVX may potentially introduce biases in the parameters that are determined using model-based algorithms, and these biases may modify the impact of age-related or therapeutic changes.

Analysis of Variance↗
PubMed2001

An update on glucocorticoid-induced osteoporosis.

In general, bone loss from glucocorticoid treatment occurs rapidly within the first 6 months of therapy. Glucocorticoids alter bone metabolism by multiple pathways; however, the bone loss is greatest in areas rich in trabecular bone. Preventive measures should be initiated early. It is the author's opinion that all subjects initiating treatment with prednisone at 7.5 mg or greater require calcium supplementation (diet plus supplement) at a dose of 1500 mg and vitamin D at a dose of 400 to 800 IU/d. If the patient is going to remain on this dose of glucocorticoid for more than 4 weeks, an antiresorptive agent should be started (e.g., estrogen, bisphosphonate, raloxifene). If a patient has established osteoporosis and is either initiating glucocorticoid therapy or is chronically treated with prednisone at 5 mg d or greater in addition to calcium and vitamin D supplementation, a potent antiresorptive agent (bisphosphonate) should be started. A bone mineral density measurement of either the lumbar spine or the hip may be helpful is assessing an individual's risk of osteoporosis, may improve compliance with treatment, and can be used to monitor the efficacy of the prescribed therapy. There is no reason to withhold treatment for glucocorticoid-induced bone loss until a bone mass measurement is taken, however. In motivated patients, a weight-bearing and resistance exercise program should be prescribed to help retain muscle strength and prevent depression. If hypercalciuria develops with glucocorticoid use, either thiazide diuretics or sodium restriction may be helpful. In patients who continue to lose bone or experience fracture's despite antiresorptive therapy while on glucocorticoids, bone-building anabolic agents (e.g., hPTH 1-34 or PTH 1-84) may be available someday soon.

Animals↗
PubMed2001

Corticosteroid osteoporosis.

Corticosteroids are widely used and effective agents for the control of many inflammatory diseases, but corticosteroid osteoporosis is a common problem associated with their long term high dose use. Prevention of corticosteroid osteoporosis is preferable to treatment of established corticosteroid bone loss. Several large double-blind controlled clinical trials in patients with corticosteroid osteoporosis have recently been published that provide new insights into its treatment. Based upon available evidence, the rank order of choice for prophylaxis would be a bisphosphonate followed by a vitamin D metabolite or an oestrogen type medication. Calcium alone appears to be unable to prevent rapid bone loss in patients starting corticosteroids, especially with prednisolone doses at 10 mg a day or greater. If an active vitamin D metabolite is used, calcium supplementation should be avoided unless dietary calcium intake is low. Hormone replacement therapy should be considered if hypogonadism is present. Since vertebral fracture is a common and important complication of high dose corticosteroid therapy, these findings suggest that rapid bone loss and hence fractures, can be prevented by prophylactic treatment. Although the follow-up data is limited, it is likely that such therapy needs to be continued beyond 12 months whilst patients continue significant doses of corticosteroid therapy.

Fractures, Bone↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗