https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(96)07088-2.pdf

Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures

The assessment of vertebral fracture by conventional radiography has been refined and improved using either semiquantitative or quantitative criteria. The inter- and intraobserver variability was determined for a semiquantitative visual approach that we routinely use in clinical studies for assessing prevalent and incident vertebral fractures. In addition, the semiquantitative approach was compared with a quantitative morphometric approach. The incidence and prevalence of vertebral fractures were determined in 57 postmenopausal women (age 65-75 years) by three independent observers. The radiographic basis for fracture definitions and the source of interobserver agreement for the semiquantitative technique. We conclude that the semiquantitative approach can be applied reliably in vertebral fracture assessment when performed using well-defined criteria.

Vertebral fracture assessment using a semiquantitative technique

The primary aim of this article is to provide an overview of perfluoroalkyl and polyfluoroalkyl substances (PFASs) detected in the environment, wildlife, and humans, and recommend clear, specific, and descriptive terminology, names, and acronyms for PFASs. The overarching objective is to unify and harmonize communication on PFASs by offering terminology for use by the global scientific, regulatory, and industrial communities. A particular emphasis is placed on long-chain perfluoroalkyl acids, substances related to the long-chain perfluoroalkyl acids, and substances intended as alternatives to the use of the long-chain perfluoroalkyl acids or their precursors. First, we define PFASs, classify them into various families, and recommend a pragmatic set of common names and acronyms for both the families and their individual members. Terminology related to fluorinated polymers is an important aspect of our classification. Second, we provide a brief description of the 2 main production processes, electrochemical fluorination and telomerization, used for introducing perfluoroalkyl moieties into organic compounds, and we specify the types of byproducts (isomers and homologues) likely to arise in these processes. Third, we show how the principal families of PFASs are interrelated as industrial, environmental, or metabolic precursors or transformation products of one another. We pay particular attention to those PFASs that have the potential to be converted, by abiotic or biotic environmental processes or by human metabolism, into long-chain perfluoroalkyl carboxylic or sulfonic acids, which are currently the focus of regulatory action. The Supplemental Data lists 42 families and subfamilies of PFASs and 268 selected individual compounds, providing recommended names and acronyms, and structural formulas, as well as Chemical Abstracts Service registry numbers. Integr Environ Assess Manag 2011;7:513–541. © 2011 SETAC

/pdf/perfluoroalkyl-and-polyfluoroalkyl-substances-in-the-5lp7s687ay.pdf

Perfluoroalkyl and polyfluoroalkyl substances in the environment: Terminology, classification, and origins

Here we report, for the first time, on the global distribution of perfluorooctanesulfonate (PFOS), a fluorinated organic contaminant. PFOS was measured in the tissues of wildlife, including, fish, birds, and marine mammals. Some of the species studied include bald eagles, polar bears, albatrosses, and various species of seals. Samples were collected from urbanized areas in North America, especially the Great Lakes region and coastal marine areas and rivers, and Europe. Samples were also collected from a number of more remote, less urbanized locations such as the Arctic and the North Pacific Oceans. The results demonstrated that PFOS is widespread in the environment. Concentrations of PFOS in animals from relatively more populated and industrialized regions, such as the North American Great Lakes, Baltic Sea, and Mediterranean Sea, were greater than those in animals from remote marine locations. Fisheating, predatory animals such as mink and bald eagles contained concentrations of PFOS that were greater than the concentrations in their diets. This suggests that PFOS can bioaccumulate to higher trophic levels of the food chain. Currently available data indicate that the concentrations of PFOS in wildlife are less than those required to cause adverse effects in laboratory animals.

http://www.usask.ca/toxicology/jgiesy/pdf/best%20paper%20awards/JA-266.pdf

Global distribution of perfluorooctane sulfonate in wildlife.

Phase 3 clinical trials, which evaluate the effect that new interventions have on the clinical outcomes of particular relevance to the patient (such as death, loss of vision, or other major symptom...

/pdf/surrogate-end-points-in-clinical-trials-are-we-being-misled-3o9o1b8e6c.pdf

Surrogate End Points in Clinical Trials: Are We Being Misled?

We assessed the rates of vertebral fracture in patients with postmenopausal osteoporosis. Forty-five patients were not treated (91 person-years of observation); 59 were treated conventionally, with calcium (alone or combined with estrogen) or vitamin D or both (218 years); and 61 were treated with sodium fluoride combined with conventional therapy (251 years). The fracture rate (per thousand person-years) was 834 in untreated patients, 419 in those given calcium with or without vitamin D, 304 in those given fluoride and calcium with or without vitamin D, 181 in those given estrogen and calcium with or without vitamin D, and 53 in those given fluoride, estrogen, and calcium with or without vitamin D. It was reduced in all treatment groups (P less than 0.001 for calcium and P less than 1 x 10(-6) for other combinations); fluoride (one years of treatment) and estrogen (but not vitamin D) independently reduced the rate from that observed with calcium alone (P less than 0.001). The combination of calcium fluoride, and estrogen was more effective than any other combination (P less than 0.001). These results provide grounds for optimism about the efficacy of combinations of available agents with sodium fluoride for fracture in postmenopausal osteoporosis.

Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis: comparison with conventional therapy

Separation of fluoride by rapid diffusion using hexamethyldisiloxane.

IT has been assumed that there is only one form of fluoride in serum, the inorganic F ion. It would therefore seem that either the value for serum fluoride which I found (1 µM) (refs. 1 and 2) or that found by Singer and Armstrong (7.5 µM) (ref. 3) must be in error. While the diffusion method of Singer and Armstrong has been shown to produce erroneous values, the same cannot be said for their ashing and distillation procedure. The evidence that the serum fluoride is about 1 µM in a fluoridated community does not rule out the possibility that more fluoride could be made available from serum by ashing; it only indicates that the fluoride in serum able to exchange with added radioactive fluoride can be measured and is 1 µM.

Donald R. Taves

Papers

Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis: comparison with conventional therapy

Separation of fluoride by rapid diffusion using hexamethyldisiloxane.

Evidence that there are two forms of fluoride in human serum.

Determination of submicromolar concentrations of fluoride in biological samples.

Serum fluoride analysis with the fluoride electrode.