Context More than 3% of adults report vitamin D intakes of 4000 IU/day or more, but the safety of this practice is unknown. Objective The objective of this work is to establish whether vitamin D doses up to 10 000 IU/day are safe and well tolerated. Design The Calgary Vitamin D Study was a 3-year, double-blind, randomized controlled trial. Setting A single-center study was conducted at the University of Calgary, Canada. Participants Participants included healthy adults (n = 373) ages 55 to 70 years with serum 25-hydroxyvitamin D 30 to 125 nmol/L. Interventions Participants were randomly assigned 1:1:1 to vitamin D3 400, 40 000, or 10 000 IU/day. Calcium supplementation was initiated if dietary calcium intake was less than 1200 mg/day. Main Outcome Measures In these prespecified secondary analyses, changes in serum 25-hydroxyvitamin D, calcium, creatinine, 24-hour urine calcium excretion, and incidence of adverse events were assessed. Between-group differences in adverse events were examined using incident rate differences and logistic regression. Results Of 373 participants (400: 124, 4000: 125, 10 000: 124), 49% were male, mean (SD) age was 64 (4) years, and 25-hydroxyvitamin D 78.0 (19.5) nmol/L. Serum calcium, creatinine, and 24-hour urine calcium excretion did not differ between treatments. Mild hypercalcemia (2.56-2.64 mmol/L) occurred in 15 (4%) participants (400: 0%, 4000: 3%, 10 000: 9%, P = .002); all cases resolved on repeat testing. Hypercalciuria occurred in 87 (23%) participants (400: 17%, 4000: 22%, 10 000: 31%, P = .01). Clinical adverse events were experienced by 365 (97.9%) participants and were balanced across treatment arms. Conclusions The safety profile of vitamin D supplementation is similar for doses of 400, 4000, and 10 000 IU/day. Hypercalciuria was common and occurred more frequently with higher doses. Hypercalcemia occurred more frequently with higher doses but was rare, mild, and transient.

Second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) provides the highest resolution in vivo to assess bone density and microarchitecture in 3D. Although strong agreement of most outcomes measured with first- (XCTI) and second- (XCTII) generation HR-pQCT has been demonstrated, the ability to use the two systems interchangeably is unknown. From in vivo measurements, we determined the limits of estimating XCTII data from XCTI scans conducted in vivo and whether that estimation can be improved by linear cross-calibration equations. These data are crucial as the research field transitions to the new technology. Our study design established cross-calibration equations by scanning 62 individuals on both systems on the same day and then tested those cross-calibrations on the same cohort 6 months later so that estimated (denoted as XCTII*) and "true" XCTII parameters could be compared. We calculated the generalized least-significant change (GLSC) for those predictions. There was strong agreement between both systems for density (R > 0.94), macroarchitecture (R > 0.95), and most microarchitecture outcomes with the exception of trabecular thickness (Tb.Th, R = 0.51 to 0.67). Linear regression equations largely eliminated the systematic error between XCTII and XCTII* and produced a good estimation of most outcomes, with individual error estimates between 0.2% and 3.4%, with the exception of Tt.BMD. Between-system GLSC was similar to within-XCTI LSC (eg, 8.3 to 41.9 mg HA/cm for density outcomes). We found that differences between outcomes assessed with XCTI and XCTII can be largely eliminated by cross-calibration. Tb.Th is poorly estimated because it is measured more accurately by XCTII than XCTI. It may be possible to use cross-calibration for most outcomes when both scanner generations are used for multicenter and longitudinal studies. © 2017 American Society for Bone and Mineral Research.

Background Periprosthetic joint infection (PJI) after hip and knee arthroplasty is a leading cause of revision surgery, inferior function, complications, and death. The administration of topical, intrawound vancomycin (vancomycin powder) has appeared promising in some studies, but others have found it ineffective in reducing infection risk; for that reason, a high-quality systematic review of the best-available evidence is needed. Questions/purposes In this systematic review, we asked: (1) Does topical vancomycin (vancomycin powder) reduce PJI risk in hip and knee arthroplasty? (2) Does topical vancomycin lead to an increased risk of complications after hip and knee arthroplasty? Methods A search of Embase, MEDLINE, and PubMed databases as of June 2020 was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies comparing topical vancomycin in addition to standard infection prevention regimens (such as routine perioperative intravenous antibiotics) with standard regimens only in primary hip and knee arthroplasty were identified. Patients 18 years or older with a minimum follow-up of 3 months were included. No restrictions on maximal loss to follow-up or PJI definition were imposed. Studies were excluded if they included patients with a history of septic arthritis, used an antibiotic other than vancomycin or a different route of administration for the intervention, performed additional interventions that differed between groups, or omitted a control group. A total of 2408 studies were screened, resulting in nine eligible studies reviewing 3371 patients who received topical vancomycin (vancomycin powder) during a primary THA or TKA and 2884 patients who did not receive it. Groups were comparable with respect to duration of follow-up and loss to follow-up when reported. Study quality was assessed using the Newcastle-Ottawa scale, showing moderate-to-high quality for the included studies. The risks of PJI and overall complications in the topical vancomycin group were compared with those in the control group. Results One of nine studies found a lower risk of PJI after primary THA or TKA, while eight did not, with odds ratios that broadly bracketed the line of no difference (range of odds ratios across the nine studies 0.09 to 1.97). In the six studies where overall complications could be compared between topical vancomycin and control groups in primary THA or TKA, there was no difference in overall complication risks with vancomycin (range of ORs across the six studies 0.48 to 0.94); however, we caution that these studies were underpowered to detect differences in the types of uncommon complications associated with vancomycin use (such as allergy, ototoxicity, and nephrotoxicity). Conclusion In the absence of clear evidence of efficacy, and without a sufficiently large evidence base reporting on safety-related endpoints, topical vancomycin (vancomycin powder) should not be used in routine primary THA and TKA. Adequately powered, multicenter, prospective trials demonstrating clear reductions in infection risk and large registry-driven audits of safety-related endpoints are required before the widespread use of topical vancomycin can be recommended. Level of Evidence Level III, therapeutic study.