A bone resorption marker as predictor of rate of change in femoral neck size and strength during the menopause transition.

We assessed whether a bone resorption marker, measured early in the menopause transition (MT), is associated with change in femoral neck size and strength during the MT. Higher levels of bone resorption were associated with slower increases in femoral neck size and faster decreases in femoral neck strength. PURPOSE: Composite indices of the femoral neck's ability to withstand compressive (compression strength index, CSI) and impact (impact strength index, ISI) forces integrate DXA-derived femoral neck width (FNW), bone mineral density (BMD), and body size. During the menopause transition (MT), FNW increases, and CSI and ISI decrease. This proof-of-concept study assessed whether a bone resorption marker, measured early in the MT, is associated with rates of change in FNW, CSI and ISI during the MT. METHODS: We used previously collected bone resorption marker (urine collagen type I N-telopeptide [U-NTX]) and femoral neck strength data from 696 participants from the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the MT in a multi-ethnic cohort of community-dwelling women. RESULTS: Adjusted for MT stage (pre- vs. early perimenopause), age, body mass index (BMI), bone resorption marker collection time, and study site in multivariable linear regression, bone resorption in pre- and early perimenopause was not associated with transmenopausal decline rate in femoral neck BMD. However, each standard deviation (SD) increase in bone resorption level was associated with 0.2% per year slower increase in FNW (p = 0.03), and 0.3% per year faster declines in CSI (p = 0.02) and ISI (p = 0.01). When restricted to women in early perimenopause, the associations of bone resorption with change in FNW, CSI, and ISI were similar to those in the full sample. CONCLUSIONS: Measuring a bone resorption marker in pre- and early perimenopause may identify women who will experience the greatest loss in bone strength during the MT.

The 25(OH)D level needed to maintain a favorable bisphosphonate response is ≥33 ng/ml.

UNLABELLED: Why only some osteoporotic patients maintain response to prolonged bisphosphonate therapy is unknown. We examined bisphosphonate response and its association with serum 25 hydroxy vitamin D (25(OH)D) level in a "real world" setting. Serum 25(OH)D level was strongly associated with maintaining bisphosphonate response arguing that vitamin D may be involved in optimizing prolonged bisphosphonate therapy. INTRODUCTION: This study examined the maintenance of bisphosphonate response in the "real world" setting and the association between 25(OH)D and bisphosphonate response using an established composite definition of response. METHODS: Postmenopausal women with low bone mineral density (BMD) treated with bisphosphonates were identified from two New York City practices. Patients were excluded for a history of chronic steroid use, metabolic bone disease, or bisphosphonate non-adherence. Patients were categorized as bisphosphonate non-responders if they had a T-score < -3 that persisted between dual-energy X-ray absorptiometry (DEXA) scans, a >3% decrease in BMD, or an incident fracture on bisphosphonate therapy, criteria based on the EUROFORS trial. Demographic and clinical data including mean 25(OH)D levels between DEXA scans were obtained. Mean 25(OH)D levels were compared between responders and non-responders and multiple logistic regression analysis was performed to identify factors associated with non-response. RESULTS: A total of 210 patients were studied. A favorable response to bisphosphonate therapy was seen in 47% (N = 99/210). Patients with a mean 25(OH)D ≥33 ng/ml had a ~4.5-fold greater odds of a favorable response (P < 0.0001). 25(OH)D level was significantly associated with response - a 1 ng/ml decrease in 25(OH)D was associated with ~5% decrease in odds of responding (odds ratio = 0.95; 95% confidence interval, 0.92-0.98; P = 0.0006). CONCLUSIONS: Patients with a mean 25(OH)D ≥33 ng/ml had a substantially greater likelihood of maintaining bisphosphonate response. This threshold level of 25(OH)D is higher than that considered adequate by the Institute of Medicine, arguing that higher levels may be required for specific therapeutic outcomes.

Dynamic compression of single cells.

OBJECTIVE: The objective of this study was to measure the effects of dynamic compression on single chondrocyte gene expression using a single cell approach, combining single cell biomechanics with single cell gene expression. DESIGN: Articular chondrocytes from the middle and deep zones of bovine distal metatarsal cartilage were statically or dynamically compressed (at a frequency of approximately 1Hz) using a custom creep cytocompression apparatus, and their gene expression levels for type II collagen, aggrecan, tissue inhibitor of metalloproteinase-1, and matrix metalloproteinase-1 were subsequently measured using single cell real-time reverse transcriptase-polymerase chain reaction. RESULTS: Single chondrocyte gene expression was lognormally distributed, suggesting that studies of populations of cells may be biased by a minority of cells with very high levels of gene expression, and would not accurately describe the behavior of most chondrocytes. Chondrocytes exposed to dynamic loading did, in general, have higher levels of type II collagen and aggrecan gene expression than statically loaded cells. Specifically, compressive forces of 50 and 100 nN suppressed type II collagen expression when applied statically, but the equivalent dynamic loads increased expression to control levels. Tissue inhibitor of metalloproteinase-1 was not affected by the mechanical loading regimens examined. CONCLUSIONS: We have demonstrated that a single cell approach is a viable methodology for studying the responses of cells to mechanical forces. Furthermore, examining the effects of mechanical loading on a cell-by-cell basis allows us to capture behaviors and details that would otherwise elude studies performed on a larger scale.

Glial growth factor-2 promotes the survival, migration and bromodeoxyuridine incorporation of mammalian neural crest cells in caudal neural tube explant cultures.

Using an in vitro assay system, we found that GGF-2 increases the number of nascent trunk neural crest cells (NCC) present in the dorsal outgrowth derived from E12 caudal neural tube explants. Data is presented which suggests that this increased outgrowth was due to a combination of GGF-2 mediated effects, including its ability to promote (A) NCC survival by decreasing the percentage of NCC that undergo cell death via a mechanism involving DNA fragmentation, (B) the initial phases of NCC migration, (C) mitosis of peripherally migrating NCC. We also show that GGF-2 can promote the long-term survival of NCC in the absence of the neural tube. An immunohistochemical analysis indicates that NCC express erbB-2 and erbB-4 neuregulin receptors.

Development and clinical evaluation of a root coverage procedure using a collagen barrier membrane.

The use of guided tissue regeneration (GTR) procedures in the treatment of gingival recession has shown promising results and is gaining clinical acceptance. The purpose of this study was to assess the use of a bioabsorbable collagen membrane as a barrier device in root coverage treatment of gingival recession defects. The study consisted of 10 patients with 10 defects of either Miller Class I or II description and gingival recession > or =2.5 mm. Clinical measurements taken at baseline included plaque index (PI) and gingival index (GI), clinical attachment level (CAL) measured with an automated probe and reference stent, recession depth (RD; mean = 3.19 +/- 0.26 mm), recession width (RW; 3.95 +/- 0.41 mm), probing depth (PD; 2.3 +/- 0.2 mm), and width of keratinized tissue (KT; 2.4 +/- 0.3 mm); measurements were repeated at 1, 2, and 4 weeks and 3 and 6 months post-treatment. During the surgical procedure, a mucoperiosteal flap was elevated and the respective root thoroughly planed. The collagen membrane was cut to cover the defect and surrounding bone, positioned over the root, and secured with 5-0 gut interdental sutures. The flap was coronally positioned to cover the membrane and sutured with 5-0 silk. Data were analyzed using the Student paired t-test to compare pre- and postsurgery measurements. The nonparametric Wilcoxon matched pairs test was used to analyze the significance of PI and GI at different time intervals. A statistically significant (P < 0.01) reduction in RD (-1.66 +/- 0.25 mm) was observed at 6 months, representing 51.6% total attainable root coverage. Clinically, a statistically significant mean gain of 1.34 +/- 0.47 mm CAL and 0.90 +/- 0.32 mm KT was observed at 6 months. No statistical differences were found in PD and RW between baseline and 6 months postoperatively. PI and GI remained low and showed no statistically significant change (P < 0.05) throughout the study period. Results from this study suggest that a collagen membrane can be used successfully as a barrier device in GTR-based root coverage procedures.

Effects of FGF-1 and FGF-2 on GD3 immunoreactive spinal neuroepithelial cells.

Embryonic central nervous system neuroepithelial cells are a transient population of cells that give rise to neuronal and glial progenitors. In the E12-E16 embryonic rat spinal neural tube we have identified neuroepithelial cells as radially oriented cells expressing the GD3 ganglioside as recognized by the monoclonal anti-GD3 ganglioside antibodies, R24 and LB1. In vitro, neuroepithelial cells, which migrate from the ventral aspect of E12 rat lumbosacral neural tube explants, also express GD3 ganglioside immunoreactivity, thus permitting their distinction from neural crest cells (NCC) which migrate from the dorsal aspect of such explants. Fibroblast growth factor-1 (FGF-1, acidic FGF) and FGF-2 (basic FGF) increase the migration of neuroepithelial cells and the extent to which they incorporate the thymidine analogue bromodeoxyuridine (BrdU). They do not, however, alter the rate at which these migrating neuroepithelial cells undergo cell death. Previous observations established the actions of FGF-1 and FGF-2 on neuronal and glial cells. The present study indicates that these growth factors also influence the motility and proliferation of progenitor cells at a developmental stage which precedes their divergence into neuronal and glial lineages.

Utilization of a resorbable collagen membrane in repairing gingival recession defects.

Predictable coverage of exposed root surfaces and the corresponding treatment of gingival recession defects remain important objectives of periodontal therapy. A variety of techniques have been developed during the past several decades to address this common clinical challenge. Traditional surgical approaches have been relatively successful in achieving root coverage. Attempts have been made recently to achieve root coverage with surgical techniques based on the principles of guided tissue regeneration, using resorbable and nonresorbable materials. The learning objective of this article is to present case documentations of root coverage, using a resorbable collagen barrier. The results achieved illustrate the potential of this material in the treatment of gingival recession. The biologic properties of collagen as a barrier material, the surgical approach, and the principles of case selection are reviewed.

Characterization of the electrophysiological, biochemical and behavioral actions of epibatidine.

Epibatidine has been reported to be a potent, nonopioid analgesic. In this study we further characterized its receptor interactions and its analgesic properties. Radioligand binding assays demonstrated that epibatidine has high affinity for nicotinic receptors (Ki = 0.12 nM) but low affinity for opioid and other receptors (Ki > 3.0 microM). In vitro functional assays demonstrated that the compound is a potent agonist at both neuronal and neuromuscular nicotinic receptors. Epibatidine depolarized rat isolated vagus nerve with an EC50 of 33.1 nM and contracted guinea pig ileum with an EC50 of 6.1 nM. Epibatidine contracted frog rectus abdominis muscle with an EC50 of 18.2 nM. In vivo, epibatidine demonstrated short-lived analgesic actions. Epibatidine (10 and 30 micrograms/kg), at 5 but not 20 min after dosing, increased the threshold for vocalization evoked by foot shock. Epibatidine, at 5 and 20 but not 60 min after dosing, also increased the latency to a nociceptive response in a hot-plate assay. Both (+)- and (-)-enantiomers of epibatidine were active in these assays. The action of epibatidine in the hot-plate test was reversed by the nicotinic receptor antagonist mecamylamine but not by the opioid receptor antagonist naloxone. In contrast to morphine, epibatidine failed to increase locomotor activity. These findings demonstrate that epibatidine is a potent agonist at both neuronal and neuromuscular nicotinic receptors. These findings also demonstrate a short-lived, naloxone-insensitive, analgesic action for both the (+)- and (-)-enantiomers of epibatidine.(ABSTRACT TRUNCATED AT 250 WORDS)