Andrew Shields

Effects of Salmon Calcitonin on Trabecular Microarchitecture as Determined by Magnetic Resonance Imaging: Results From the QUEST Study

The unique noninvasive MRI technique was used to assess trabecular microarchitecture at multiple skeletal sites in 91 postmenopausal osteoporotic women receiving nasal spray salmon calcitonin (CT‐NS) or placebo over 2 years. In the distal radius and lower trochanter of the hip, individuals treated with CT‐NS exhibited significant preservation of trabecular bone microarchitecture compared with placebo, where significant deterioration was shown. MRI analyses of os calcis or μCT/histomorphometric analyses of bone biopsies did not reveal consistent differences in architecture between CT‐NS and placebo.

ASSESSMENT OF BONE QUALITY, QUANTITY, AND TURNOVER WITH MULTIPLE METHODOLOGIES AT MULTIPLE SKELETAL SITES

The risk for osteoporotic fracture, and presumably the therapeutic prevention of such risk by osteoporosis therapies, is determined primarily by the parameters of bone quality (principally trabecular architecture and strength), bone quantity (bone mineral density), and bone turnover (markers of bone resorption such as pyridinolines and telopeptides). Other contributors are age, bone geometry (particularly of the femoral neck), and (extrinsic to the skeleton) falls. It is unclear as to the relative contributions of each of the intrinsic parameters to fracture risk, and particularly to the therapeutic prevention of such risk. Recent evidence1indicates that the therapeutic prevention of fracture is mediated to only a small extent by changes in quality; and there is a growing consensus that changes in turnover2 are equally important to changes in quantity to fracture reduction following osteoporosis therapies. The comparatively new hypothesis is that therapeutic prevention of osteoporotic fracture may be equally due to preservation or improvements in bone quality (trabecular architecture, strength, and material properties), based upon recent data with both raloxifene3 and salmon-calcitonin4 in which significant reduction in vertebral fracture is associated with only modest effects on bone quantity and turnover.

Diagnosis of postmenopausal osteoporosis: reviews in endocrine and metabolic disorders.

The diagnostic evaluation of postmenopausal osteoporosis may be divided into (1) diagnosing the disease (i.e., postmenopausal osteoporosis as characterized by low bone mineral density [BMD] with or without fracture), (2) excluding other medical conditions which may display these ®ndings of osteoporosis (low BMD, osteoporotic fracture) as an accompanying disorder, and (3) de®ning the risk of osteoporosis (i.e., the risk of low BMD and/or fracture). For the generalist, and for the osteoporosis specialist, this diagnostic evaluation is facilitated by the medical history, the physical examination, and the laboratory evaluation (blood and urine tests including markers of bone turnover, and radiographic (spine X-ray, bone densitometry and ultrasoundÐUS)) and invasive (bone biopsy) technologies): i.e., diagnosing the disease is facilitated with skeletal X-ray and bone densitometry/US, exclusion of other medical conditions by medical history and laboratory evaluation including bone biopsy, and risk assessment by the medical history (risk factors), bone densitometry, US, and bone markers. While the history and physical examination, and much of the laboratory evaluation, is relatively straight forward and requires only an overview for purposes of this review, a more detailed assessment of bone densitometry and ultrasound, and of bone turnover markers, is warranted.

Test-retest reproducibility of FDG-PET/CT uptake in cancer patients within a qualified and calibrated local network

Calibration and reproducibility of quantitative 18F-FDG PET measures are essential for adopting integral 18F-FDG PET/CT biomarkers and response measures in multicenter clinical trials. We implemented a multicenter qualification process using National Institute of Standards and Technology–traceable reference sources for scanners and dose calibrators, and similar patient and imaging protocols. We then assessed SUV in patient test–retest studies. Methods: Five 18F-FDG PET/CT scanners from 4 institutions (2 in a National Cancer Institute–designated Comprehensive Cancer Center, 3 in a community-based network) were qualified for study use. Patients were scanned twice within 15 d, on the same scanner (n = 10); different but same model scanners within an institution (n = 2); or different model scanners at different institutions (n = 11). SUVmax was recorded for lesions, and SUVmean for normal liver uptake. Linear mixed models with random intercept were fitted to evaluate test–retest differences in multiple lesions per patient and to estimate the concordance correlation coefficient. Bland–Altman plots and repeatability coefficients were also produced. Results: In total, 162 lesions (82 bone, 80 soft tissue) were assessed in patients with breast cancer (n = 17) or other cancers (n = 6). Repeat scans within the same institution, using the same scanner or 2 scanners of the same model, had an average difference in SUVmax of 8% (95% confidence interval, 6%–10%). For test–retest on different scanners at different sites, the average difference in lesion SUVmax was 18% (95% confidence interval, 13%–24%). Normal liver uptake (SUVmean) showed an average difference of 5% (95% confidence interval, 3%–10%) for the same scanner model or institution and 6% (95% confidence interval, 3%–11%) for different scanners from different institutions. Protocol adherence was good; the median difference in injection-to-acquisition time was 2 min (range, 0–11 min). Test–retest SUVmax variability was not explained by available information on protocol deviations or patient or lesion characteristics. Conclusion: 18F-FDG PET/CT scanner qualification and calibration can yield highly reproducible test–retest tumor SUV measurements. Our data support use of different qualified scanners of the same model for serial studies. Test–retest differences from different scanner models were greater; more resolution-dependent harmonization of scanner protocols and reconstruction algorithms may be capable of reducing these differences to values closer to same-scanner results.