Estimating osteoporotic fracture risk following a wrist fracture: a tale of two systems

© 2015, The Author(s). Summary: The WHO fracture risk assessment (FRAX) and Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tools can both be used to determine an individual’s 10-year risk of osteoporotic fracture. However, these tools differ in their risk calculation. For participants fracture, FRAX provides a lower fracture risk estimate than CAROC resulting in fewer decisions to initiate therapy.Purpose: The purpose of the current report is to compare fracture risk prediction rates using the CAROC and the FRAX® tools.Methods: Individuals ≥50 years with a distal radius fracture resulting from a fall from standing height or less were recruited from a single orthopedic clinic. Participants underwent a DXA scan of their lumbar spine and hip. Femoral neck (FN) bone mineral density (BMD) and fracture risk factors were used to determine each participant’s 10-year fracture risk using both fracture risk assessment tools. Participants were categorized as low (\u3c10 \u3e%), moderate (10–20 %), or high (\u3e20 %) risk. Stratified by age (\u3c65 \u3eyears, \u3e65 years), the proportion of participants in each category was compared between the tools.Results: Analyses included 60 participants (mean age 65.7 ± 9.6 years). In those (n = 26), the proportion of individuals at low, moderate, and high risk differed between the FRAX and CAROC tools (p \u3c 0.0001). FRAX categorized 69 % as low (CAROC 0 %) and 3 % as high (CAROC 12 %) risk. For individuals \u3e65 years, almost all were at least at moderate risk (FRAX 79 %, CAROC 53 %), but fewer were at high risk using FRAX (18 vs. 47 %, p \u3c 0.0003).Conclusion: For participants 65 years were at moderate or high risk under both FRAX and CAROC and should at least be considered for pharmacotherapy

Appropriate Osteoporosis Treatment by Family Physicians inResponse to FRAX vs CAROC Reporting: Results Froma Randomized Controlled Trial

© 2014 The International Society for Clinical Densitometry. Canadian guidelines recommend either the FRAX or the Canadian Association of Radiologists and Osteoporosis Canada (CAROC) fracture risk assessment tools to report 10-yr fracture risk as low (20%). It is unknown whether one reporting system is more effective in helping family physicians (FPs) identify individuals who require treatment. Individuals ≥50yr old with a distal radius fracture and no previous osteoporosis diagnosis or treatment were recruited. Participants underwent a dual-energy x-ray absorptiometry scan and answered questions about fracture risk factors. Participants\u27 FPs were randomized to receive either a FRAX report or the standard CAROC-derived bone mineral density report currently used by the institution. Only the FRAX report included statements regarding treatment recommendations. Within 3 mo, all participants were asked about follow-up care by their FP, and treatment recommendations were compared with anosteoporosis specialist. Sixty participants were enrolled (31 to FRAX and 29 to CAROC). Kappa statistics of agreement in treatment recommendation were 0.64 for FRAX and 0.32 for bone mineral density. The FRAX report was preferred by FPs and resulted in better postfracture follow-up and treatment that agreed more closely with a specialist. Either the clear statement of fracture risk or the specific statement of treatment recommendations on the FRAX report may have supported FPs to make better treatment decisions

Management of osteoporosis in men: an update and case example

In 2002, Osteoporosis Canada published clinical practice guidelines for the diagnosis and management of osteoporosis. The current paper supplements that guideline and provides a review and synthesis of the current literature on the diagnosis and management of osteoporosis in men

Functional Analysis of a Type 1 Parathyroid Hormone Receptor Intracellular Tail Mutant [KRK(484-6)AAA]: Effects on Second Messenger Generation and Cellular Targeting

The parathyroid hormone receptor type 1 (PTHR1) is activated by parathyroid hormone (PTH) and PTH-related protein (PTHrP) and primarily signals via intracellular pathways involving adenylyl cyclase and phospholipase C. The intracellular tail domain of the PTHR1 contributes to G protein subunit coupling that is important for second messenger signalling. In addition, the intracellular domain has a potential nuclear localization sequence (NLS) that, if functional, could point to an intracrine role for the receptor. In the present study, we have utilized 2 sets of constructs that employ either a [KRK(484-486)AAA](3Ala) mutation in the putative NLS or the non-mutant counterpart and included (a) the full-length rat PTHR1 with FLAG and c-myc epitope tags at the N-terminus and C-terminus, respectively (designated as PTHR1(3Ala)-TAG and PTHR1-TAG); and (b) only the putative NLS-containing intracellular domain (471-488), with green fluorescent protein (GFP) fused to the C-terminus (designated as GFP-(3Ala)471-488 or GFP-471-488). Porcine kidney LLC-PK1 cells stably expressing the PTHR1(3Ala)-TAG exhibited reduced signalling via both cAMP and cytosolic calcium transients in spite of greater cell surface expression relative to cells expressing PTHR1-TAG. We also examined the ability of the intracellular tail to influence the cellular localization of a heterologous protein. LLC-PK1 cells transiently transfected with GFP-471-488, exhibited increased fluorescence within the nucleus, relative to cells transfected with GFP alone that was not observed when cells were transiently transfected with the mutated construct, GFP-(3Ala)471-488. However, LLC-PK1 cells transiently transfected with either the full-length PTHR1-TAG or the PTHR1(3Ala)-TAG constructs did not exhibit nuclear localization of these receptors. Moreover, mouse osteoblast-like cells (MC3T3-E1) transiently expressing PTHR1-TAG also failed to demonstrate nuclear localization, although both full-length PTHR1 constructs exhibited plasma membrane immunofluorescence in both cell lines. Thus, the 484-486 sequence is critical for the full signalling responsiveness of the intact PTHR1, but the putative nuclear localization signal may not function as such within the intact receptor

Frequency of bone mineral density testing in adult kidney transplant recipients from Ontario, Canada: a population-based cohort study

Abstract Background We lack consensus on the clinical value, frequency, and timing of bone mineral density (BMD) testing in kidney transplant recipients. This study sought to determine practice patterns in BMD testing across kidney transplant centres in Ontario, Canada, and to compare the frequency of testing in kidney transplant recipients to non-transplant reference groups. Methods Using healthcare databases from Ontario, Canada we conducted a population-based cohort study of adult kidney transplant recipients who received a transplant from 1994-2009. We used logistic regression to determine if there was a statistically significant difference across transplant centres in the decision to perform at least one BMD test after transplantation, adjusting for covariates that may influence a physician’s decision to order a BMD test. We used the McNemar’s test to compare the number of recipients who had at least one BMD test to non-transplant reference groups (matching on age, sex, and date of cohort entry). Results In the first 3 years after transplant, 4821 kidney transplant recipients underwent 4802 BMD tests (median 1 test per recipient, range 0 to 6 tests), costing $600,000 (2014 CAD equivalent dollars). Across the six centres, the proportion of recipients receiving at least one BMD test varied widely (ranging from 15.6 to 92.1 %; P < 0.001). Over half (58 %) of the recipients received at least one BMD test post-transplant, a value higher than two non-transplant reference groups (general population with a previous non-vertebral fracture [hip, forearm, proximal humerus], 13.8 %; general population with no previous non-vertebral fracture, 8.5 %; P value <0.001 for each of the comparisons). Conclusions There is substantial practice variability in BMD testing after transplant. New high-quality information is needed to inform the utility, optimal timing, and frequency of BMD testing in kidney transplant recipients