Sanford Baim

Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Pediatric Position Development Conference.

The International Society for Clinical Densitometry (ISCD) convenes a Position Development Conference (PDC) every 2 yr to make recommendations for standards in the field of bone densitometry. The recommendations are based on clinically relevant issues in bone densitometry such as quality control, acquisition, analysis, interpretation, and reporting. In 2007, ISCD convened its first Pediatric Position Development Conference to address issues specific to the assessment of skeletal health in children and adolescents. Topics for consideration are developed by the ISCD Board of Directors and its Scientific Advisory Committee. Clinically relevant questions related to each topic area are assigned to task forces for a comprehensive review of the medical literature and subsequent presentation of the reports to an international panel of experts. For this PDC, the Expert Panel included representatives of the American Society for Bone and Mineral Research and International Bone and Mineral Society. The recommendations of the PDC Expert Panel are then reviewed by the ISCD Board of Directors. Recommendations that are approved become Official Positions of the ISCD. The Pediatric PDC was held June 20-21, 2007, in Montreal, Quebec, Canada. Topics considered were restricted to children and adolescents, and included DXA prediction of fracture and definition of osteoporosis; DXA assessment in diseases that may affect the skeleton; DXA interpretation and reporting; and peripheral quantitative computed tomography measurement. This report describes the methodology and results of the 2007 Pediatric PDC, and a summary of all ISCD Official Positions, including the ones recently adopted by this 2007 Pediatric PDC and the 2007 Lansdowne, Virginia, USA Adult PDC.

International Society for Clinical Densitometry 2007 Adult and Pediatric Official Positions

The International Society for Clinical Densitometry (ISCD) periodically convenes Position Development Conferences (PDCs) in order to establish standards and guidelines for the assessment of skeletal health. The most recent Adult PDC was held July 20-22, 2007, in Lansdowne, Virginia, USA; the first Pediatric PDC was June 20-21, 2007 in Montreal, Quebec, Canada. PDC topics were selected according to clinical relevancy, perceived need for standardization, and likelihood of achieving agreement. Each topic area was assigned to a task force for a comprehensive review of the scientific literature. The findings of the review and recommendations were presented to adult and pediatric international panels of experts. The panels voted on the appropriateness, necessity, quality of the evidence, strength, and applicability (worldwide or variable according to local requirements) of each recommendation. Those recommendations that were approved by the ISCD Board of Directors become Official Positions. This is a review of the methodology of the PDCs and selected ISCD Official Positions.

Precision assessment and radiation safety for dual-energy X-ray absorptiometry: position paper of the International Society for Clinical Densitometry.

Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis, assess the risk of fracture, and monitor changes in BMD over time. Because biological changes in BMD are usually small in proportion to the error inherent in the test itself, interpretation of serial BMD tests depends on knowledge of the smallest change in BMD that is beyond the range of error. This value, called the least significant change (LSC), varies according to the instrument used, the patient population being tested, the measurement site, the skill of the technologist at positioning the patient and analyzing the test, and the confidence interval used in the calculation. The precision and LSC values provided by the manufacturer cannot be applied to clinical bone densitometry centers because of the differences in the patients being tested and the technologist performing the test. Because harmful errors in clinical management may occur from incorrectly interpreting serial BMD tests, it is recommended that every DXA technologist conduct a precision assessment and calculate the LSC for each measurement site and DXA instrument used. Precision assessment provides direct benefit to patients by allowing clinicians to make clinical decisions based on genuine change or stability of BMD. The patient-care benefits of precision assessment outweigh the risk of exposure to trivial doses of ionizing radiation.

Executive Summary of the 2013 International Society for Clinical Densitometry Position Development Conference on Body Composition

There have been many scientific advances in measurement of fat and lean body mass as determined by dual-energy X-ray absorptiometry (DXA). The International Society for Clinical Densitometry (ISCD) convened a Position Development Conference (PDC) on the use of DXA for body composition measurement. Previously, no guidelines to the use of DXA for body composition existed. The recommendations pertain to clinically relevant issues regarding DXA indications of use, acquisition, analysis, quality control, interpretation, and reporting were addressed. The topics and questions for consideration were developed by the ISCD Board of Directors and the Scientific Advisory Committee and were designed to address the needs of clinical practitioners. Three Task Forces were created and assigned these questions and asked to conduct comprehensive literature reviews. The Task Forces included participants from 6 countries and a variety of interests including academic institutions, private clinics, and industry. Reports with proposed Position Statements were then presented to an international panel of experts with backgrounds in DXA and bone densitometry and a variety of fields that use body composition measures. The PDC was held in Tampa, FL, contemporaneously with the Annual Meeting of the ISCD, March 21 through March 23, 2013. This report describes the methodology of the 2013 ISCD Body Composition PDC and summarizes the results. Three separate articles in this issue will detail the rationale, discussion, and additional research topics for each question the Task Forces addressed.

National Osteoporosis Foundation 2008 Clinician's Guide to Prevention and Treatment of Osteoporosis and the World Health Organization Fracture Risk Assessment Tool (FRAX): What They Mean to the Bone Densitometrist and Bone Technologist

The long-awaited update of the National Osteoporosis Foundation (NOF) 2003 Physician’s Guide to Prevention and Treatment of Osteoporosis (1) (Physician’s Guide) was released on February 21, 2008. The new guide (2), Clinician’s Guide to Prevention and Treatment of Osteoporosis (Clinician’s Guide), is available online at http://www.nof.org and is expected to be in print later this year. The new recommendations include use of the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) to determine a patient’s 10-year risk of hip and major osteoporosis-related fractures and review the cost-effective thresholds for treatment intervention. The FRAX model is available online at http:// www.shef.ac.uk/FRAX and was released for public use the same day as the new NOF Guidelines (Figs. 1 and 2). We will explore the implications of FRAX and the new NOF guidelines as they relate to clinical densitometry. The NOF Clinician’s Guide is a comprehensive set of recommendations on prevention, diagnosis, and treatment of osteoporosis in men age 50 years and older and postmenopausal women of all ethnicities. It includes information on epidemiology, whom to test, whom to treat, and therapeutic options. Recommendations for pharmacologic treatment are based in part on the US adaptation of the WHO 10-year fracture probability model (3) that includes US hip fracture incidence and mortality rates and algorithms that incorporate the costs and health consequences of clinical osteoporotic fractures (4). The NOF Clinician’s Guide suggests that treatment recommendations be

Conversion of the lac repressor into an allosterically regulated transcriptional activator for mammalian cells.

A novel mammalian regulatory system was created by using the Escherichia coli lac repressor. The lac repressor was converted into a mammalian transcriptional activator by modifying the lac repressor coding region to include a nuclear localization signal from the simian virus 40 (SV40) large tumor antigen and the transcription activation domain from the herpes simplex virus type 1 virion protein 16. The lac activator protein (LAP) fusions were potent activators of several promoters containing lac operator sequences positioned either upstream or downstream of the transcription unit. A single lac operator allowed for transactivation, whereas multiple operators acted synergistically when separated by a small distance. Promoters containing 14 or 21 operator sequences were induced at least 1,000-fold in response to LAP, reaching levels of activity 20 to 30 times greater than that of the SV40 early promoter in HeLa cells. Activation was strongly inhibited by isopropyl-beta-D-thiogalactoside (IPTG), indicating that LAP retained the functions needed for allosteric regulation. LAP was bifunctional, also acting as a repressor of expression of an SV40 promoter containing an operator immediately downstream of the TATA box. Finally, genetic selection schemes were developed such that LAP-expressing cell lines can be generated at high frequency from either established or primary cells in culture.

A mutation allowing an mRNA secondary structure diminishes translation of Saccharomyces cerevisiae iso-1-cytochrome c.

The CYC1-239-O mutation in the yeast Saccharomyces cerevisiae produces a -His-Leu- replacement of the normal -Ala-Gly- sequence at amino acid positions 5 and 6, which lie within a dispensable region of iso-1-cytochrome c; this mutation can accommodate the formation of a hairpin structure at the corresponding site in the mRNA. The amount of the altered protein was diminished to 20% of the wild-type level, whereas the amount of the mRNA remained normal. However, in contrast to the normal CYC1+ mRNA that is associated mainly with four to seven ribosomes, the bulk of the CYC1-239-O mRNA is associated with one to four ribosomes. These results suggest that the stable secondary structure within the translated region of the CYC1 mRNA diminishes translation by inhibiting elongation.

Assessing the clinical utility of serum CTX in postmenopausal osteoporosis and its use in predicting risk of osteonecrosis of the jaw.

Bone turnover markers (BTMs) have become increasingly important in the management of postmenopausal osteoporosis (PMO). In bisphosphonate‐treated women with PMO, BTMs can provide early indications of treatment efficacy, are predictors of BMD response and fracture risk reduction, and are potentially useful for monitoring patient compliance. The bone resorption marker serum C‐telopeptide cross‐link of type 1 collagen (sCTX) has shown high sensitivity and specificity for the detection of increased bone resorption. Recently, sCTX has been singled out as a potential indicator of risk of osteonecrosis of the jaw (ONJ) in patients receiving oral bisphosphonates who require oral surgery. However, whether BTMs are capable of predicting ONJ risk and whether sCTX is usable for this purpose are controversial questions. This article presents an overview of the current literature regarding critical issues affecting the clinical utility of BTMs (including variability and reference ranges) and the current applications of BTMs in PMO management, with a focus on sCTX. Last, the appropriateness of using sCTX to predict ONJ risk in women receiving oral bisphosphonates for PMO is evaluated.

Special report on the 2007 adult and pediatric Position Development Conferences of the International Society for Clinical Densitometry.

The International Society for Clinical Densitometry (ISCD) conducts Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines in the field of bone densitometry. Topics for consideration are selected according to clinical relevance, a perceived need for standardization, and the likelihood of achieving agreement. Questions regarding nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests for each topic area are assigned to task forces for a comprehensive review of the scientific literature. The findings of the review and recommendations are then presented to an international panel of experts at the PDC. The expert panel votes on potential Official Positions for appropriateness, necessity, quality of the evidence, strength of the recommendation, and applicability (worldwide or variable according to local requirements). Recommendations that are approved by the ISCD Board of Directors become Official Positions. The first Pediatric PDC was 20–21 June 2007 in Montreal, QC, Canada. The most recent Adult PDC was held 20–22 July 2007, in Lansdowne, VA, USA. This Special Report summarizes the methodology of the ISCD PDCs and presents selected Official Positions of general interest.

Primary Care Use of FRAX®: Absolute Fracture Risk Assessment in Postmenopausal Women and Older Men

Abstract Osteoporosis-related fractures (low-trauma or fragility fractures) cause substantial disability, health care costs, and mortality among postmenopausal women and older men. Epidemiologic studies indicate that at least half the population burden of osteoporosis-related fractures affects persons with osteopenia (low bone density), who comprise a larger segment of the population than those with osteoporosis. The public health burden of fractures will fail to decrease unless the subset of patients with low bone density who are at increased risk for fracture are identified and treated. Risk stratification for medically appropriate and cost-effective treatment is facilitated by the World Health Organization (WHO) FRAX® algorithm, which uses clinical risk factors, bone mineral density, and country-specific fracture and mortality data to quantify a patients 10-year probability of a hip or major osteoporotic fracture. Included risk factors comprise femoral neck bone mineral density, prior fractures, parental hip fracture history, age, gender, body mass index, ethnicity, smoking, alcohol use, glucocorticoid use, rheumatoid arthritis, and secondary osteoporosis. FRAX® was developed by the WHO to be applicable to both postmenopausal women and men aged 40 to 90 years; the National Osteoporosis Foundation Clinicians Guide focuses on its utility in postmenopausal women and men aged > 50 years. It is validated to be used in untreated patients only. The current National Osteoporosis Foundation Guide recommends treating patients with FRAX® 10-year risk scores of ≥ 3% for hip fracture or ≥ 20% for major osteoporotic fracture, to reduce their fracture risk. Additional risk factors such as frequent falls, not represented in FRAX®, warrant individual clinical judgment. FRAX® has the potential to demystify fracture risk assessment in primary care for patients with low bone density, directing clinical fracture prevention strategies to those who can benefit most.