Using 3D image registration to maximize the reproducibility of longitudinal bone strength assessment by HR-pQCT and finite element analysis.

We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D image registration to account for misalignment between images. This reduced variability in longitudinal FE estimates and improved our ability to measure in vivo changes in HR-pQCT studies of bone strength. INTRODUCTION: We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D rigid-body registration (3DR) to maximize reproducibility by accounting for misalignment between images. METHODS: In our proposed approach, we used the full common bone volume defined by 3DR to estimate standard FE parameters. Using standard HR-pQCT imaging protocols, we validated the 3DR approach with ex vivo samples of the distal radius (n = 10, four repeat scans) by assessing whether 3DR can reduce measurement variability from repositioning error. We used in vivo data (n = 40, five longitudinal scans) to assess the sensitivity of 3DR to detect changes in bone strength at the distal radius by the standard deviation of the rate of change (σ), where the ideal value of σ is minimized to define true change. FE estimates by 3DR were compared to estimates by no registration (NR) and slice-matching (SM). RESULTS: Group-wise comparisons of ex vivo variation (CVRMS, %) found that FE measurement precision was improved by SM (CVRMS < 0.80%) and 3DR (CVRMS < 0.62%) compared to NR (CVRMS~2%), and 3DR was advantageous as repositioning error increased. Longitudinal in vivo reproducibility was minimized by 3DR for failure load estimates (σ = 0.008 kN/month). CONCLUSION: Although 3D registration cannot negate motion artifacts, it plays an important role in detecting and reducing variability in FE estimates for longitudinal HR-pQCT data and is well suited for estimating effects of interventions in in vivo longitudinal studies of bone strength.

Pharmacotherapy decisions among postmenopausal women attending a group medical consultation or a one-on-one specialist consultation at an osteoporosis center: an observational cohort study.

Group medical visits for osteoporosis can improve access to care while being highly accepted by patients. In this study, a similar proportion of women planned to initiate pharmacotherapy after attending a group or traditional one-on-one osteoporosis consultation, indicating that the group consultation model does not produce unexpected treatment decisions. INTRODUCTION: Group medical consultations for osteoporosis are time-efficient and highly accepted by patients, but effects on treatment decisions are unknown. We aimed to compare women's decisions to initiate or decline osteoporosis pharmacotherapy after attending either a group or transitional one-on-one osteoporosis consultation. METHODS: In this observational study, we prospectively evaluated postmenopausal women referred to an osteoporosis clinic who attended a group medical visit and compared their decisions regarding pharmacologic osteoporosis treatment with retrospective data from a cohort of women who attended a traditional consultation. Both consultation types involved interaction with a specialist physician, individualized fracture risk estimation (using FRAX®), and education regarding fracture consequences and available osteoporosis medications. Both forms of consultation emphasized shared decision-making; however, group consultation attendees did not receive personalized treatment recommendations from the physician. RESULTS: We reviewed the records of 125 women (median age 63 years) who attended a group consultation and 83 women (median age 64 years) who attended a traditional consultation between 2016 and 2019. Twenty-four (19%) of the group cohort and 16 (19%) of the traditional cohort were at high 10-year risk of major osteoporotic fracture (FRAX® ≥ 20.0%). A similar proportion planned to initiate pharmacologic therapy after the group and traditional consultations (23% vs 16%, p = 0.22); these proportions were comparable among women at high risk (42% vs 50%, p = 0.75) and moderate risk (19% vs 15%, p = 0.77), but a higher proportion of low-risk women planned to initiate therapy after the group consultation (18% vs 0%, p = 0.009). CONCLUSION: Patient decisions to initiate pharmacologic treatment made during a group visit are similar to those made during traditional one-on-one consultation. The group consultation model represents an alternative to one-on-one assessment for delivering osteoporosis consultative services.

Simulated effects of early menopausal bone mineral density preservation on long-term fracture risk: a feasibility study.

Prevention of early menopausal bone loss may reduce the future burden of osteoporosis. In this modelling exercise, an osteoporosis prevention strategy involving 5-year infusions of zoledronic acid, beginning early in menopause, reduced long-term fracture risk and the proportion of aging women with femoral neck densitometric osteoporosis. This strategy warrants further evaluation. INTRODUCTION: Preventing early menopausal bone loss may substantially reduce the future burden of osteoporosis. We modelled the effects of infrequent zoledronic acid infusions on long-term fracture risk. METHODS: Data from the Canadian Multicentre Osteoporosis Study (CaMos) were used to determine the expected natural history of femoral neck areal bone mineral density (BMD) and fracture risk (using FRAX®) from ages 50-80 for women with no antiresorptive drug exposures. We modelled the effects of three infusions of zoledronic acid (at ages 50, 55, 60) on long-term fracture risk, assuming this intervention would preserve BMD until age 65 years, followed by losses mirroring early menopausal BMD loss. RESULTS: At age 65, untreated women and zoledronic acid recipients had expected mean (SD) femoral neck T-scores of - 1.5(1.0) and - 0.8(1.0), 10-year major osteoporotic fracture (MOF) risks of 9.8%(5.0) and 8.0%(3.7) and hip fracture risks of 1.7%(2.4) and 0.8%(1.2), respectively. At age 80, untreated women and zoledronic acid recipients had expected femoral neck T-scores of - 1.9(0.9) and - 1.4(0.9), MOF risks of 17.9%(8.2) and 14.9%(6.4) and hip fracture risks of 6.3%(6.2) and 4.4%(4.5), respectively. The expected proportion of women with femoral neck T-score ≤ - 2.5 was 14.9% for untreated women and 3.8% for zoledronic acid recipients at age 65, increasing to 28.1% and 12.0%, respectively, at age 80. Numbers-needed-to-treat to prevent one case of densitometric osteoporosis were 9 at age 65 and 5 at age 80. CONCLUSION: Infrequent infusions of zoledronic acid, initiated early in menopause, are expected to reduce long-term fracture risk and result in a substantial reduction in the proportion of women with densitometric osteoporosis after age 65.

Effect of high-dose vitamin D supplementation on peripheral arterial calcification: secondary analysis of a randomized controlled trial.

Although high-dose vitamin D supplementation is common, effects on arterial calcification remain unexplored. Tibial artery calcification was identified and quantified over 3 years in participants randomized to 400, 4000, or 10,000 IU vitamin D3 daily. High-dose vitamin D supplementation did not affect the development or progression of arterial calcification. INTRODUCTION: To determine whether vitamin D supplementation has a dose-dependent effect on development and progression of arterial calcification. METHODS: This was a secondary analysis of the Calgary Vitamin D Study, a 3-year, double-blind, randomized controlled trial conducted at a single-center in Calgary, Canada. Participants were community-dwelling adults aged 55-70 years with serum 25-hydroxyvitamin D 30-125 nmol/L. Participants were randomized 1:1:1 to receive vitamin D3 400, 4000, or 10,000 IU/day for 3 years. Tibial artery calcification was identified and quantified (in milligrams of hydroxyapatite, mgHA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6, 12, 24, and 36 months. Changes in calcification over time and treatment group interaction were evaluated using a constrained linear mixed effects model. RESULTS: Of 311 randomized participants, 302 (400: 105, 4000: 96, 10,000: 101) were eligible for analysis of arterial calcification (54% male, mean (SD) age 62 (4) years, mean (SD) 25-hydroxyvitamin D 78.9 (19.9) nmol/L). At baseline, 85 (28%) had tibial artery calcification, and mean (95% CI) calcification quantity was 2.8 mgHA (95% CI 1.7-3.9). In these 85 participants, calcification quantity increased linearly by 0.020 mgHA/month (95% CI 0.012-0.029) throughout the study, with no evidence of a treatment-group effect (p = 0.645 for interaction). No participants developed new arterial calcifications during the study. CONCLUSIONS: In this population of community-dwelling adults who were vitamin D replete at baseline, supplementation with vitamin D 400, 4000, or 10,000 IU/day did not have differential effects on the development or progression of arterial calcification over 3 years. TRIAL REGISTRATION: clinicaltrials.gov (NCT01900860).

Longitudinal bone microarchitectural changes are best detected using image registration.

Longitudinal studies of bone using high-resolution medical imaging may result in non-physiological measurements of longitudinal changes. In this study, we determined that three-dimensional image processing techniques best capture realistic longitudinal changes in bone density and should therefore be used with high-resolution imaging when studying bone changes over time. INTRODUCTION: The purpose of this study was to determine which longitudinal analysis technique (no registration (NR), slice-match (SM) registration, or three-dimensional registration (3DR)) produced the most realistic longitudinal changes in a 3-year study of bone density and structure using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: We assessed HR-pQCT scans of the distal radius and tibia for men and women (N = 40) aged 55-70 years at baseline and 6, 12, 24, and 36 months. To evaluate which longitudinal analysis technique (NR, SM, or 3DR) best captured physiologically reasonable 3-year changes, we calculated the standard deviation of the absolute rate of change in each bone parameter. The data were compared between longitudinal analysis techniques using repeated measures ANOVA and post hoc analysis. RESULTS: As expected, both SM and 3DR better captured physiological longitudinal changes than NR. At the tibia, there were no differences between SM and 3DR; however, at the radius where precision was lower, 3DR produced better results for total bone mineral density. CONCLUSIONS: At least SM or 3DR should be implemented in longitudinal studies using HR-pQCT. 3DR is preferable, particularly at the radius, to ensure that physiological changes in bone density are observed.

Long-term hypovitaminosis D and secondary hyperparathyroidism outcomes of the Roux-en-Y gastric bypass: a systematic review.

INTRODUCTION: Pre-operative Vitamin D deficiency is markedly prevalent in prospective bariatric surgery patients. While bariatric surgery leads to significant weight loss, it can exacerbate or prolong Vitamin D deficiency. We systematically reviewed the literature to assess whether secondary hyperparathyroidism is maintained in the medium to long term in patients following the Roux-en-Y gastric bypass. METHODS: A comprehensive literature search was conducted through Medline, Embase, Scopus, Web of Science, Dare, Cochrane library and HTA database. The search terms used were bariatric surgery, gastric bypass and hyperparathyroidism. RESULTS: Fourteen studies were included (n = 2688 subjects). Parathyroid hormone levels rose gradually from a mean pre-operative level of 5.69 ± 1.2 pmol/L to 6.36 ± 0.77 pmol/L, 7.59 ± 0.73 pmol/L and 8.29 ± 1.41 pmol/L at 2 years, between 2 and 5 years, and beyond 5 years, respectively. Vitamin D levels slowly fell to a mean of 20.50 ± 4.37 ng/mL and 20.76 ± 3.80 ng/mL between follow-up intervals 2-5 years and beyond 5, respectively. CONCLUSION: It appears that hyperparathyroidism persists at 5-year follow-up after gastric bypass, despite most patients being supplemented with calcium and Vitamin D.

Effect of single-dose dexamethasone on acute phase response following zoledronic acid: a randomized controlled trial.

Zoledronic acid provokes an inflammatory reaction, or acute phase response, in some individuals. We examined whether treatment with dexamethasone could prevent this response. A single dose of dexamethasone 4 mg, given at the time of zoledronic acid infusion, did not influence the incidence or severity of the acute phase response. INTRODUCTION: The potent bisphosphonate zoledronic acid (ZOL) is used to treat osteoporosis, Paget's disease, and hypercalcemia of malignancy. This medication can provoke an inflammatory reaction, known as the acute phase response (APR). We examined whether glucocorticoid treatment at the time of first exposure to ZOL prevents the development of APR. METHODS: This double-blind, randomized, controlled trial assessed 40 adults receiving ZOL 5 mg intravenously for the first time. Participants received oral dexamethasone 4 mg (n = 20) or placebo (n = 20) at the time of ZOL infusion. Oral temperature was measured at baseline and three times a day for 3 days following infusion. Symptoms of APR were assessed via questionnaire at baseline then daily for 3 days and again at day 15 post-infusion. Use of rescue medications (paracetamol or ibuprofen) in the 3 days following infusion was evaluated. Primary outcome was between-group difference in temperature change from baseline. RESULTS: There was no significant difference in temperature change (p = 0.95) or symptom score (p = 0.42) in the 3 days following ZOL between dexamethasone and placebo recipients. Eleven (55%) in the dexamethasone group and 10 (50%) placebo recipients experienced a temperature increase of ≥1 °C (p = 0.99). Seven (35%) in the dexamethasone group and 9 (45%) in the placebo group experienced an increase in symptom score of ≥3 points (p = 0.75). Thirteen (65%) dexamethasone recipients and 12 (60%) in the placebo group required rescue medications (p = 0.99). Dexamethasone was well-tolerated. CONCLUSIONS: A single dose of dexamethasone 4 mg does not influence the incidence or severity of APR following first exposure to ZOL. TRIAL REGISTRATION: ACTRN12615000794505.

Acute effects of calcium supplements on blood pressure: randomised, crossover trial in postmenopausal women.

Calcium supplements appear to increase cardiovascular risk, but the mechanism is unknown. We investigated the acute effects of calcium supplements on blood pressure in postmenopausal women. The reduction in systolic blood pressure was smaller after calcium compared with the placebo in the hours following dosing. INTRODUCTION: Calcium supplements appear to be associated with increased cardiovascular risk; however, the mechanism of this is uncertain. We previously reported that blood pressure declined over a day in older women, and that this reduction was smaller following a calcium supplement. To confirm this finding, we investigated the acute effects of calcium supplements on blood pressure. METHODS: This was a randomised controlled crossover trial in 40 healthy postmenopausal women (mean age 71 years and BMI 27.2 kg/m2). Women attended on two occasions, with visits separated by ≥7 days. At each visit, they received either 1 g of calcium as citrate, or placebo. Blood pressure and serum calcium concentrations were measured immediately before, and 2, 4 and 6 h after each intervention. RESULTS: Ionised and total calcium concentrations increased after calcium (p < 0.0001 versus placebo). Systolic blood pressure decreased after both calcium and placebo, but significantly less so after calcium (p = 0.02). The reduction in systolic blood pressure from baseline was smaller after calcium compared with placebo by 6 mmHg at 4 h (p = 0.036) and by 9 mmHg at 6 h (p = 0.002). The reduction in diastolic blood pressure was similar after calcium and placebo. CONCLUSIONS: These findings are consistent with those of our previous trial and indicate that the use of calcium supplements in postmenopausal women attenuates the post-breakfast reduction in systolic blood pressure by around 6-9 mmHg. Whether these changes in blood pressure influence cardiovascular risk requires further study.

Incidence, risk factors, and outcomes for Enterococcus spp. blood stream infections: a population-based study.

BACKGROUND: Enterococci are a clinically significant cause of bloodstream infections (BSI), particularly in the nosocomial setting. The purpose of this study was to characterize the incidence, risk factors for acquisition, microbiological characteristics and mortality of enterococcal BSI within the well-defined population of a large Canadian health region. METHODS: Surveillance for all episodes of enterococcal BSI occurring among residents of the Calgary Health Zone (population 1.2 million) between 2000 and 2008 was conducted using an electronic surveillance system. Clinical features, microbiology, and outcomes were obtained. RESULTS: A total of 710 incident episodes of enterococcal BSI were identified for an annual incidence of 6.9 episodes per 100,000; the incidences of E. faecalis and E. faecium BSI were 4.5, and 1.6 per 100,000, respectively. Enterococcus faecalis infections were associated with a urinary focus, genitourinary malignancy, and abnormal genitourinary anatomy. E. faecium infections were associated with a gastrointestinal focus. Resistance to ampicillin, vancomycin and ciprofloxacin was higher in E. faecium infection. The overall case fatality rate was 22.8%, and was higher for E. faecium infection. CONCLUSIONS: This is the second population-based study to assess the risk factors for enterococcal BSI and compare the characteristics of infection with E. faecalis and E. faecium. Results suggest that BSI with E. faecalis and E. faecium should be regarded as two clinically different entities with unique sets of risk factors and microbiologic characteristics.