Determinants of imminent fracture risk in postmenopausal women with osteoporosis.

In elderly women with osteoporosis, prior fracture, low BMD, impaired physical functioning, poorer general health, and recent falls were all direct predictors of imminent (in next year) fracture risk. Prior fracture, older age, worse health, impaired cognitive functioning, and recent falls indirectly increased imminent risk by reducing physical functioning/general health. INTRODUCTION: This study was designed to examine determinants of imminent risk of osteoporotic fracture (i.e., next 1-2 years) in postmenopausal women. METHODS: This retrospective cohort study used data from Caucasian women age 65 or older with osteoporosis who participated in the observational Study of Osteoporotic Fractures (SOF). We examined potential direct and indirect predictors of hip and nonvertebral fractures in 1-year follow-up intervals including anthropometric measures, bone mineral density (T-score), fracture since age 50, physical function, cognition, medical conditions, recent (past year) falls, and lifestyle factors. Clinically related variables were grouped into constructs via factor analysis. These constructs and selected individual variables were incorporated into a theoretical structural equation model to evaluate factors that influence imminent risk. RESULTS: Among 2261 patients, 19.4% had a nonvertebral fracture and 5.5% had a hip fracture within 1 year of a study visit between 1992 and 2008. Prior fracture, lower T-scores, lower physical functioning, and recent falls all directly increased 1-year risk of nonvertebral fracture. For both nonvertebral and hip fractures, prior fracture and recent falls influenced risk indirectly through general health, while cognition influenced risk via physical functioning. Age influenced both physical functioning and general health. CONCLUSIONS: Several established risk factors for 10-year fracture risk also played a role in predicting imminent risk of fracture (e.g., T-scores, prior fracture), as did falls, cognition, physical functioning, and general health. Fracture risk assessments should also consider falls and fall risk factors as well as established bone-related risk factors in assessing imminent fracture risk.

Teriparatide treatment patterns in osteoporosis and subsequent fracture events: a US claims analysis.

UNLABELLED: The objective of this study was to describe the risk of fragility-related fractures in the 2 years following teriparatide initiation. In an administrative claims analysis of over 11,407 patients, approximately one in eight patients had a new or recurrent fragility-related fracture in the 2 years following teriparatide initiation. INTRODUCTION: The objective of this study was to describe the risk of fragility-related fractures in the 2 years following the initiation of teriparatide in a real-world setting. METHODS: This retrospective study used data from the 2002 to 2011 MarketScan® Commercial and Medicare Supplemental Databases to identify patients 50 years and older with a diagnosis of osteoporosis (ICD-9-CM code 733.0x) who were initiating teriparatide. Patients were required to have continuous medical and pharmacy benefit coverage for the 12 months prior to and 24 months following teriparatide initiation (index event). Teriparatide treatment patterns (persistence and adherence) were described, as was the use of antiresorptive therapy. The primary study outcome was the presence of a new or recurring fragility fracture following the initiation of teriparatide. RESULTS: A total of 11,407 patients met the study criteria (mean age = 69.5, standard deviation = 10.6 years; 92.0% female). One in four (25.6%) patients had fragility fracture claims in the year prior to teriparatide initiation, of which 64.0% were on existing antiresorptive therapy. Overall, 13.4% (n = 1527) of patients had a new or recurrent fracture during the 2-year follow-up period. Forty-eight percent of patients on teriparatide treatment were considered persistent; fragility fractures were more common among patients nonpersistent with teriparatide (15.2%) than among those persistent with teriparatide (11.4%). A higher fracture rate (35.7%) was observed in the cohort with previous fragility fracture then those without pre-index fractures (24%). CONCLUSION: More than 13.4% of patients had new or recurrent fragility-related fractures during the 2 years following the initiation of teriparatide; these fractures were more in common in patients with pre-existing fractures and the patients who were nonpersistent with teriparatide.

Pathophysiology of septic shock and implications for therapy.

Current knowledge about the pathophysiology of septic shock is reviewed, and biotechnology-based therapies under development are discussed. Patients with septic shock begin their clinical course with leukocytosis, fever, tachycardia, tachypnea, and organ hypoperfusion; shock ensues as immunologic and vasoactive mediators produce hypotension. There are many metabolic and cardiovascular responses, and single- or multiple-organ failure is common. Patients may experience adult respiratory distress syndrome. A multitude of endogenous and exogenous factors have been linked to the pathophysiology of sepsis and septic shock, including (1) endotoxin from gram-negative bacteria, (2) peptidoglycan and exotoxins from gram-negative bacteria, (3) endotoxin-binding proteins and receptors, (4) bactericidal proteases, (5) exotoxins from gram-positive bacteria, (6) acute-phase proteins and proteases, (7) cytokines, (8) arachidonic acid metabolites, (9) complement, (10) beta-endorphin, (11) histamine, (12) stimulation of intrinsic and extrinsic coagulation pathways and proteases, and (13) endothelium-derived factors and adhesion molecules. Molecular entities and strategies under development to combat septic shock include monoclonal antibodies to endotoxin, active immunization with lipid-A analogues, bactericidal permeability-increasing protein, interleukin inhibitors, and inhibitors of tumor necrosis factor-alpha. Successful treatment of septic shock will probably require a combination of agents, including antimicrobials. An ideal goal for biotechnology in the area of septic shock is to prevent invading pathogens from overstimulating the host's immune system and to systematically eliminate those pathogens. Biotechnology is opening new avenues to the treatment of septic shock.

Natural products and the athlete: facts and folklore.

OBJECTIVE: To contrast scientific facts with suggested manufacturers' claims regarding food supplements (natural products) marketed for enhanced athletic prowess. DATA SOURCES: A MEDLINE search was performed to obtain documentation supporting the claims of natural-product manufacturers. In addition, several references pertaining to pharmacognosy, natural products, herbs, pharmacy practice, and sports medicine were reviewed. Claims were obtained from promotional advertisements in bodybuilding magazines, product labels, and fact sheets for sales representatives in nutrition and health-food stores. DATA EXTRACTION: We reviewed all of the clinical trials, published between 1966 and 1992, relative to the manufacturers' claims regarding these products. DATA SYNTHESIS: Pertinent human and/or animal studies supporting each natural product were compared with the manufacturers' claims. CONCLUSIONS: We found that there was no published scientific evidence to support the promotional claims for a large proportion of the products (8/19, 42 percent). Only 4 of 19 products (21 percent) were associated with any documented human clinical trials supporting their promotional claims. Six of 19 agents (32 percent) had some scientific documentation to support their promotional claims; however, these products were judged to be marketed in a misleading manner.