Effect of Vitamin D3 Supplementation on Acute Fracture Healing: A Phase II Screening Randomized Double-Blind Controlled Trial.

Nearly half of adult fracture patients are vitamin D deficient (serum 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Many surgeons advocate prescribing vitamin D supplements to improve fracture healing outcomes; however, data supporting the effectiveness of vitamin D3 supplements to improve acute fracture healing are lacking. We tested the effectiveness of vitamin D3 supplementation for improving tibia and femur fracture healing. We conducted a single-center, double-blinded phase II screening randomized controlled trial with a 12-month follow-up. Patients aged 18-50 years receiving an intramedullary nail for a tibia or femoral shaft fracture were randomized 1:1:1:1 to receive (i) 150,000 IU loading dose vitamin D3 at injury and 6 weeks (n = 27); (ii) 4000 IU vitamin D3 daily (n = 24); (iii) 600 IU vitamin D3 daily (n = 24); or (iv) placebo (n = 27). Primary outcomes were clinical fracture healing (Function IndeX for Trauma [FIX-IT]) and radiographic fracture healing (Radiographic Union Score for Tibial fractures [RUST]) at 3 months. One hundred two patients with a mean age of 29 years (standard deviation 8) were randomized. The majority were male (69%), and 56% were vitamin D3 deficient at baseline. Ninety-nine patients completed the 3-month follow-up. In our prespecified comparisons, no clinically important or statistically significant differences were detected in RUST or FIX-IT scores between groups when measured at 3 months and over 12 months. However, in a post hoc comparison, high doses of vitamin D3 were associated with improved clinical fracture healing relative to placebo at 3 months (mean difference [MD] 0.90, 80% confidence interval [CI], 0.08 to 1.79; p = 0.16) and within 12 months (MD 0.89, 80% CI, 0.05 to 1.74; p = 0.18). The study was designed to identify potential evidence to support the effectiveness of vitamin D3 supplementation in improving acute fracture healing. Vitamin D3 supplementation, particularly high doses, might modestly improve acute tibia or femoral shaft fracture healing in healthy adults, but confirmatory studies are required. The Vita-Shock trial was awarded the Orthopaedic Trauma Association's (OTA) Bovill Award in 2020. This award is presented annually to the authors of the most outstanding OTA Annual Meeting scientific paper. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Study protocol: design and rationale for an exploratory phase II randomized controlled trial to determine optimal vitamin D3 supplementation strategies for acute fracture healing.

BACKGROUND: Observational studies have found that 75% of healthy adult fracture patients (ages 18-50) have serum 25-hydroxyvitamin D (25(OH)D) levels < 30 ng/mL. Although lower serum 25(OH)D levels have yet to be correlated to fracture healing complications or poor fracture outcomes, many orthopedic surgeons are routinely prescribing vitamin D supplements to improve fracture healing in healthy non-osteoporotic patients. To address this gap in the literature, we propose a phase II exploratory randomized controlled trial comparing three vitamin D3 dosing regimens for early surrogate treatment response. METHODS: We will conduct a 4-arm blinded exploratory phase II trial in 96 adults aged 18-50 years with a closed or low-grade open (Gustilo type I or II) tibial or femoral shaft fracture. Eligible patients will be randomized in equal allocation ratio of 1:1:1:1 to one of the treatment groups: (1) 150,000 IU loading dose vitamin D3 plus daily dose placebo; (2) loading dose placebo plus 4000 IU vitamin D3 per day, (3) loading dose placebo plus 600 IU vitamin D3 per day, or (4) loading dose placebo plus daily dose placebo. The primary outcome is fracture healing, assessed as follows: (1) clinical fracture healing measured using the Function IndeX for Trauma, (2) radiographic fracture healing measured using the Radiographic Union Score for Tibial fractures, and (3) biological fracture healing measured using serum levels of cross-linked C-terminal telopeptides of type I collagen and amino-terminal procollagen propeptides of collagen type I. The main secondary outcome will be assessed by measuring serum 25(OH)D levels. All outcome analyses will be exploratory and adhere to the intention-to-treat principle. Per-protocol sensitivity analyses will also be conducted. DISCUSSION: Study results will be disseminated through a publication in an academic journal and presentations at orthopedic conferences. Study results will inform dose selection for a large definitive randomized controlled trial and provide preliminary clinical data on which dose may improve acute fracture healing outcomes in healthy adult patients (18-50 years) at 3 months. TRIAL REGISTRATION: Vita-Shock (A Blinded Exploratory Randomized Controlled Trial to Determine Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing) was registered at ClinicalTrials.gov (identifier NCT02786498) prior to enrollment of participants.

Glucocorticoid induced osteoporosis.

INTRODUCTION: Glucocorticoid-induced osteoporosis is the most common secondary cause of osteoporosis. Despite this, many patients receiving glucocorticoids are not evaluated for their skeletal health. AREAS COVERED: Glucocorticoids have profound effects on bone cells, resulting in increases in bone resorption and impairments in bone formation. Bone loss and subsequent increases in fracture risk occur early after the administration of glucocorticoids. Incidence of fractures is highest within the first 6 months of glucocorticoid treatment, and declines with longer exposure. Decreases in bone mass follow a dose-dependent relationship with glucocorticoid dosage. Pharmacologic prevention and treatment for osteoporosis are recommended for all patients receiving glucocorticoids. Oral bisphosphonates, with concomitant vitamin D and calcium supplementation, are considered as the first-line treatment option. However, a number of alternative treatment options, including intravenous bisphosphonates, anabolic agents, and denosumab have all proven efficacy in increasing lumbar spine or hip bone mineral density. The mechanism of action and recent controlled trials for these therapies are reviewed. The literature search was conducted within PubMed in November 2018. 492 articles were found and 45 were included. EXPERT OPINION: Future studies will likely evaluate the safety profiles of alternative treatments, while focusing on its ability to reduce fracture risk.

Getting fit for hip and knee replacement: a protocol for the Fit-Joints pilot randomized controlled trial of a multi-modal intervention in frail patients with osteoarthritis.

BACKGROUND: Joint replacement provides significant improvements in pain, physical function, and quality of life in patients with osteoarthritis. With a growing body of evidence indicating that frailty can be treated, it is important to determine whether targeting frailty reduction in hip and knee replacement patients improves post-operative outcomes. OBJECTIVES: The primary objective is to examine the feasibility of a parallel group RCT comparing a preoperative multi-modal frailty intervention to usual care in pre-frail/frail older adults undergoing elective unilateral hip or knee replacements. The secondary objectives areTo explore potential efficacy of the multi-modal frailty intervention in improving frailty and mobility between baseline and 6 weeks post-surgery using Fried frailty phenotype and short performance physical battery (SPPB) respectively.To explore potential efficacy of the multi-modal frailty intervention on post-operative healthcare services use. METHODS/DESIGN: In a parallel group pilot RCT, participants will be recruited from the Regional Joint Assessment Program in Hamilton, Canada. Participants who are (1) ≥ 60 years old; (2) pre-frail (score of 1 or 2) or frail (score of 3-5; Fried frailty phenotype); (3) having elective unilateral hip or knee replacement; and (4) having surgery wait times between 3 and 10 months will be recruited and randomized to either the intervention or usual care group. The multi-modal frailty intervention components will include (1) tailored exercise program (center-based and/or home-based) with education and cognitive behavioral change strategies; (2) protein supplementation; (3) vitamin D supplementation; and (4) medication review. The main comparative analysis will take place at 6 weeks post-operative. The outcome assessors, data entry personnel, and data analysts are blinded to treatment allocation. Assessments: feasibility will be assessed by recruitment rate, retention rate, and data collection completion. Frailty and healthcare use and other clinical outcomes will be assessed. The study outcomes will be collected at the baseline, 1 week pre-operative, and 6 weeks and 6 months post-operative. DISCUSSION: This is the first study to examine the feasibility of multi-modal frailty intervention in pre-frail/frail older adults undergoing hip or knee replacement. This study will inform the planning and designing of multi-modal frailty interventional studies in hip and knee replacement patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02885337.

Patient preferences for nutritional supplementation to improve fracture healing: a discrete choice experiment.

OBJECTIVE: Vitamin D is often prescribed as an adjuvant therapy to aid fracture healing due to its biological role in bone health. However, the optimal frequency, dosage and duration of vitamin D supplementation for non-osteoporotic fracture healing has not been established. The objective of this study was to determine patient preferences for fracture healing relative to hypothetical vitamin D supplementation dosing options. DESIGN: Discrete choice experiment. SETTING: Level 1 trauma centre in Baltimore, Maryland, USA. PARTICIPANTS: 199 adult (18-60 years) patients with a fracture. PRIMARY OUTCOME MEASURES: Parameter estimates of utility for fracture healing relative to dosing regimens were analysed using hierarchical Bayesian modelling. RESULTS: A reduced risk of reoperation (34.3%) and reduced healing time (24.4%) were the attributes of greatest relative importance. The highest mean utility estimates were for a one-time supplementation dose (ß=0.71, 95% CI 0.41 to 1.00) followed by a reduced risk of reoperation (ß=0.41 per absolute % reduction, 95% CI 0.0.36 to 0.46). Supplementation for 24 weeks in duration (ß=-0.83, 95% CI -1.00 to -0.67) and a daily supplement (ß=-0.29, 95% CI -0.47 to -0.11) had the lowest mean utilities. The 'no supplement' option had a large negative value suggesting supplementation was generally desirable in this sample population. Among other possible clinical scenarios, patients expected a 2% reduction in the absolute risk of reoperation or a 3.1-week reduction in healing time from the baseline to accept a treatment regimen requiring two separate doses of supplementation, two blood tests and a cost of $20 within 3 months of injury. CONCLUSIONS: Patients with orthopaedic trauma demonstrated strong willingness to take a vitamin D supplement that would decrease risk of reoperation and reduce healing time. Furthermore, these findings specify the required decrease in reoperation risk and reduction in healing time patients would expect to adhere to possible vitamin D dosing regimens.

Efficacy of a biomechanically-based yoga exercise program in knee osteoarthritis: A randomized controlled trial.

OBJECTIVE: Certain exercises could overload the osteoarthritic knee. We developed an exercise program from yoga postures with a minimal knee adduction moment for knee osteoarthritis. The purpose was to compare the effectiveness of this biomechanically-based yoga exercise (YE), with traditional exercise (TE), and a no-exercise attention-equivalent control (NE) for improving pain, self-reported physical function and mobility performance in women with knee osteoarthritis. DESIGN: Single-blind, three-arm randomized controlled trial. SETTING: Community in Southwestern Ontario, Canada. PARTICIPANTS: A convenience sample of 31 women with symptomatic knee osteoarthritis was recruited through rheumatology, orthopaedic and physiotherapy clinics, newspapers and word-of-mouth. INTERVENTIONS: Participants were stratified by disease severity and randomly allocated to one of three 12-week, supervised interventions. YE included biomechanically-based yoga exercises; TE included traditional leg strengthening on machines; and NE included meditation with no exercise. Participants were asked to attend three 1-hour group classes/sessions each week. MEASUREMENTS: Primary outcomes were pain, self-reported physical function and mobility performance. Secondary outcomes were knee strength, depression, and health-related quality of life. All were assessed by a blinded assessor at baseline and immediately following the intervention. RESULTS: The YE group demonstrated greater improvements in KOOS pain (mean difference of 22.9 [95% CI, 6.9 to 38.8; p = 0.003]), intermittent pain (mean difference of -19.6 [95% CI, -34.8 to -4.4; p = 0.009]) and self-reported physical function (mean difference of 17.2 [95% CI, 5.2 to 29.2; p = 0.003]) compared to NE. Improvements in these outcomes were similar between YE and TE. However, TE demonstrated a greater improvement in knee flexor strength compared to YE (mean difference of 0.1 [95% CI, 0.1 to 0.2]. Improvements from baseline to follow-up were present in quality of life score for YE and knee flexor strength for TE, while both also demonstrated improvements in mobility. No improvement in any outcome was present in NE. CONCLUSIONS: The biomechanically-based yoga exercise program produced clinically meaningful improvements in pain, self-reported physical function and mobility in women with clinical knee OA compared to no exercise. While not statistically significant, improvements in these outcomes were larger than those elicited from the traditional exercise-based program. Though this may suggest that the yoga program may be more efficacious for knee OA, future research studying a larger sample is required. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02370667).

A Missed Opportunity in Bone Health: Vitamin D and Calcium Use in Elderly Femoral Neck Fracture Patients Following Arthroplasty.

INTRODUCTION: Introduction: Adequate calcium and vitamin D from diet and supplementation is recommended for elderly hip fracture patients. Using data from the multinational hip fracture arthroplasty trial (HEALTH), we determined the proportion of patients who consistently took vitamin D and calcium and which characteristics/prescribing practices were associated with consistency of supplement use. METHODS: HEALTH is a multicenter randomized trial of elderly hip fracture patients treated with hemi-arthroplasty and total hip arthroplasty. Patients were categorized as consistent users, inconsistent users, or nonusers of calcium and vitamin D. We used multinomial regression to determine the characteristics associated with calcium and vitamin D use. RESULTS: 603 HEALTH participants were included in the analysis. 34.7% of patients never took vitamin D within 12 months after surgery, 26.2% took vitamin D inconsistently, and 39.1% took vitamin D consistently. 36.0% of patients never took calcium within 12 months after surgery, 28.4% took calcium inconsistently, and 35.7% took calcium consistently. There was great variation in prescribed/recommended doses. Compared to nonusers, consistent users of the supplements were more likely to be female, North American, prescribed/recommended vitamin D and/or calcium postoperatively, and presented to a facility with comprehensive fragility fracture protocols. CONCLUSIONS: A low proportion of elderly hip fracture patients are consistently taking vitamin D and calcium, which may contribute to poorer bone health. Surgeons should be educated to prescribe/ recommend vitamin D and calcium, institutions should develop comprehensive fragility fracture protocols and patient education strategies to ensure that patients with osteoporosis receive bone health management beyond fracture care.

Rationale and design of MUSIC OS-EU: an international observational study of the treatment of postmenopausal women for osteoporosis in Europe and Canada.

OBJECTIVES: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS-EU) was designed to better understand the rate and burden of gastrointestinal (GI) events on clinical and health care outcomes among postmenopausal women with osteoporosis. METHODS: MUSIC OS-EU is a prospective, multinational, observational cohort study of postmenopausal women ≥50 years of age diagnosed with osteoporosis and enrolled in physician clinics in six countries: France, Italy, the Netherlands, Sweden, the United Kingdom, and Canada. The MUSIC OS-EU study has three components: (i) a physician survey to describe their management of osteoporotic patients with GI events; (ii) a retrospective chart survey to describe the receipt and type of osteoporosis medication prescribed; and (iii) a prospective cohort study including untreated and treated patients diagnosed with osteoporosis to investigate the rate of GI events and association with osteoporosis medication use patterns, health-related quality of life, treatment satisfaction and resource utilisation among postmenopausal women with osteoporosis. RESULTS: Physicians at 97 sites completed the physician questionnaire and data for 716 patients were abstracted for the retrospective chart review. Enrolment and the baseline data collection for the prospective cohort study were conducted between March 2012 and June 2013 for 292 untreated and 2,959 treated patients, of whom 684 were new users and 2,275 were experienced users of oral osteoporosis medications. CONCLUSIONS: The results of MUSIC OS-EU will illuminate the association of GI events with the management of osteoporosis and with patient-reported outcomes among postmenopausal women with osteoporosis in Europe and Canada.

Successful knowledge translation intervention in long-term care: final results from the vitamin D and osteoporosis study (ViDOS) pilot cluster randomized controlled trial.

BACKGROUND: Few studies have systematically examined whether knowledge translation (KT) strategies can be successfully implemented within the long-term care (LTC) setting. In this study, we examined the effectiveness of a multifaceted, interdisciplinary KT intervention for improving the prescribing of vitamin D, calcium and osteoporosis medications over 12-months. METHODS: We conducted a pilot, cluster randomized controlled trial in 40 LTC homes (21 control; 19 intervention) in Ontario, Canada. LTC homes were eligible if they had more than one prescribing physician and received services from a large pharmacy provider. Participants were interdisciplinary care teams (physicians, nurses, consultant pharmacists, and other staff) who met quarterly. Intervention homes participated in three educational meetings over 12 months, including a standardized presentation led by expert opinion leaders, action planning for quality improvement, and audit and feedback review. Control homes did not receive any additional intervention. Resident-level prescribing and clinical outcomes were collected from the pharmacy database; data collectors and analysts were blinded. In addition to feasibility measures, study outcomes were the proportion of residents taking vitamin D (≥800 IU/daily; primary), calcium ≥500 mg/day and osteoporosis medications (high-risk residents) over 12 months. Data were analyzed using the generalized estimating equations technique accounting for clustering within the LTC homes. RESULTS: At baseline, 5,478 residents, mean age 84.4 (standard deviation (SD) 10.9), 71% female, resided in 40 LTC homes, mean size = 137 beds (SD 76.7). In the intention-to-treat analysis (21 control; 19 intervention clusters), the intervention resulted in a significantly greater increase in prescribing from baseline to 12 months between intervention versus control arms for vitamin D (odds ratio (OR) 1.82, 95% confidence interval (CI): 1.12, 2.96) and calcium (OR 1.33, 95% CI: 1.01, 1.74), but not for osteoporosis medications (OR 1.17, 95% CI: 0.91, 1.51). In secondary analyses, excluding seven nonparticipating intervention homes, ORs were 3.06 (95% CI: 2.18, 4.29), 1.57 (95% CI: 1.12, 2.21), 1.20 (95% CI: 0.90, 1.60) for vitamin D, calcium and osteoporosis medications, respectively. CONCLUSIONS: Our KT intervention significantly improved the prescribing of vitamin D and calcium and is a model that could potentially be applied to other areas requiring quality improvement. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01398527 . Registered: 19 July 2011.

Characterizing the assessment and management of vitamin d levels in patients with osteoporosis in clinical practice: a chart review initiative.

Though vitamin D is important for bone health, little is known about the monitoring and management of vitamin D levels in patients with osteoporosis in clinical practice-a deficit this chart review initiative aimed to remedy. A total of 52 physicians completed profiles for 983 patients being treated for osteoporosis between November 2008 and April 2009. Information collected included demographics; fracture risk factors; availability and level of serum vitamin D measurements; and information on osteoporosis medications and calcium and vitamin D supplementation. Physicians also evaluated patients' current regimens and detailed proposed changes, if applicable. Nearly 85% of patients were prescribed calcium and vitamin D supplements. Serum 25-hydroxy vitamin D levels were available for 73% of patients. Of these patients, approximately 50% had levels less than 80 nmol/L, which contrasts with the 37% thought to have "unsatisfactory" vitamin D levels based on physician perceptions. Physicians felt 26% of patients would benefit from additional vitamin D supplementation. However, no changes to the osteoporosis regimen were suggested for 48% of patients perceived to have "unsatisfactory" vitamin D levels. The results underscore the importance of considering vitamin D status when looking to optimize bone health.

Efficacy of vitamin D supplementation in depression in adults: a systematic review.

CONTEXT: Randomized controlled trials (RCTs) investigating the efficacy of vitamin D (Vit D) in depression provided inconsistent results. OBJECTIVE: We aim to summarize the evidence of RCTs to assess the efficacy of oral Vit D supplementation in depression compared to placebo. DATA SOURCES: We searched electronic databases, two conference proceedings, and gray literature by contacting authors of included studies. STUDY SELECTION: We selected parallel RCTs investigating the effect of oral Vit D supplementation compared with placebo on depression in adults at risk of depression, with depression symptoms or a primary diagnosis of depression. DATA EXTRACTION: Two reviewers independently extracted data from relevant literature. DATA SYNTHESIS: Classical and Bayesian random-effects meta-analyses were used to pool relative risk, odds ratio, and standardized mean difference. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: Six RCTs were identified with 1203 participants (72% females) including 71 depressed patients; five of the studies involved adults at risk of depression, and one trial used depressed patients. Results of the classical meta-analysis showed no significant effect of Vit D supplementation on postintervention depression scores (standardized mean difference = -0.14, 95% confidence interval = -0.41 to 0.13, P = .32; odds ratio = 0.93, 95% confidence interval = 0.54 to 1.59, P = .79). The quality of evidence was low. No significant differences were demonstrated in subgroup or sensitivity analyses. Similar results were found when Bayesian meta-analyses were applied. CONCLUSIONS: There is insufficient evidence to support the efficacy of Vit D supplementation in depression symptoms, and more RCTs using depressed patients are warranted.

Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol.

BACKGROUND: The role of vitamin D in management of depression is unclear. Results from observational and emerging randomized controlled trials (RCTs) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association. METHODS/DESIGN: The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors' original definition. Secondary aims include assessing the change in quality of life, adverse events and treatment discontinuation. We will conduct the systematic review and meta-analysis according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present), PsychINFO (1967 to present) and ClinicalTrials.gov. Unpublished work will be identified by searching two major conferences: the International Vitamin Conference, the Anxiety Disorders and Depression Conference, while grey literature will be acquired by contacting authors of included studies. We will use the random-effects meta-analysis to synthesize the data by pooling the results of included studies. DISCUSSION: The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant settings. STUDY REGISTRATION: Unique identifier: CRD42013003849.

Calcium and vitamin D intake and mortality: results from the Canadian Multicentre Osteoporosis Study (CaMos).

CONTEXT: Calcium and vitamin D are recommended for bone health, but there are concerns about adverse risks. Some clinical studies suggest that calcium intake may be cardioprotective, whereas others report increased risk associated with calcium supplements. Both low and high serum levels of 25-hydroxyvitamin D have been associated with increased mortality. OBJECTIVE: The purpose of this study was to determine the association between total calcium and vitamin D intake and mortality and heterogeneity by source of intake. DESIGN: The Canadian Multicentre Osteoporosis Study cohort is a population-based longitudinal cohort with a 10-year follow-up (1995-2007). SETTING: This study included randomly selected community-dwelling men and women. PARTICIPANTS: A total of 9033 participants with nonmissing calcium and vitamin D intake data and follow-up were studied. EXPOSURE: Total calcium intake (dairy, nondairy food, and supplements) and total vitamin D intake (milk, yogurt, and supplements) were recorded. OUTCOME: The outcome variable was all-cause mortality. RESULTS: There were 1160 deaths during the 10-year period. For women only, we found a possible benefit of higher total calcium intake, with a hazard ratio of 0.95 (95% confidence interval, 0.89-1.01) per 500-mg increase in daily calcium intake and no evidence of heterogeneity by source; use of calcium supplements was also associated with reduced mortality, with hazard ratio of 0.78 (95% confidence interval, 0.66-0.92) for users vs nonusers with statistically significant reductions remaining among those with doses up to 1000 mg/d. These associations were not modified by levels of concurrent vitamin D intake. No definitive associations were found among men. CONCLUSIONS: Calcium supplements, up to 1000 mg/d, and increased dietary intake of calcium may be associated with reduced risk of mortality in women. We found no evidence of mortality benefit or harm associated with vitamin D intake.

Accumulation of bone strontium measured by in vivo XRF in rats supplemented with strontium citrate and strontium ranelate.

Strontium ranelate is an approved pharmacotherapy for osteoporosis in Europe and Australia, but not in Canada or the United States. Strontium citrate, an alternative strontium salt, however, is available for purchase over-the-counter as a nutritional supplement. The effects of strontium citrate on bone are largely unknown. The study's objectives were 1) to quantify bone strontium accumulation in female Sprague Dawley rats administered strontium citrate (N=7) and compare these levels to rats administered strontium ranelate (N=6) and vehicle (N=6) over 8 weeks, and 2) to verify an in vivo X-ray fluorescence spectroscopy (XRF) system for measurement of bone strontium in the rat. Daily doses of strontium citrate and strontium ranelate were determined with the intention to achieve equivalent amounts of elemental strontium. However, post-hoc analyses of each strontium compound conducted using energy dispersive spectrometry microanalysis revealed a higher elemental strontium concentration in strontium citrate than strontium ranelate. Bone strontium levels were measured at baseline and 8 weeks follow-up using a unique in vivo XRF technique previously used in humans. XRF measurements were validated against ex vivo measurements of bone strontium using inductively coupled plasma mass spectrometry. Weight gain in rats in all three groups was equivalent over the study duration. A two-way ANOVA was conducted to compare bone strontium levels amongst the three groups. Bone strontium levels in rats administered strontium citrate were significantly greater (p<0.05) than rats administered strontium ranelate and vehicle. ANCOVA analyses were performed with Sr dose as a covariate to account for differences in strontium dosing. The ANCOVA revealed differences in bone strontium levels between the strontium groups were not significant, but that bone strontium levels were still very significantly greater than vehicle.

An interdisciplinary knowledge translation intervention in long-term care: study protocol for the vitamin D and osteoporosis study (ViDOS) pilot cluster randomized controlled trial.

BACKGROUND: Knowledge translation (KT) research in long-term care (LTC) is still in its early stages. This protocol describes the evaluation of a multifaceted, interdisciplinary KT intervention aimed at integrating evidence-based osteoporosis and fracture prevention strategies into LTC care processes. METHODS AND DESIGN: The Vitamin D and Osteoporosis Study (ViDOS) is underway in 40 LTC homes (n = 19 intervention, n = 21 control) across Ontario, Canada. The primary objectives of this study are to assess the feasibility of delivering the KT intervention, and clinically, to increase the percent of LTC residents prescribed ≥800 IU of vitamin D daily. Eligibility criteria are LTC homes that are serviced by our partner pharmacy provider and have more than one prescribing physician. The target audience within each LTC home is the Professional Advisory Committee (PAC), an interdisciplinary team who meets quarterly. The key elements of the intervention are three interactive educational sessions led by an expert opinion leader, action planning using a quality improvement cycle, audit and feedback reports, nominated internal champions, and reminders/point-of-care tools. Control homes do not receive any intervention, however both intervention and control homes received educational materials as part of the Ontario Osteoporosis Strategy. Primary outcomes are feasibility measures (recruitment, retention, attendance at educational sessions, action plan items identified and initiated, internal champions identified, performance reports provided and reviewed), and vitamin D (≥800 IU/daily) prescribing at 6 and 12 months. Secondary outcomes include the proportion of residents prescribed calcium supplements and osteoporosis medications, and falls and fractures. Qualitative methods will examine the experience of the LTC team with the KT intervention. Homes are centrally randomized to intervention and control groups in blocks of variable size using a computer generated allocation sequence. Randomization is stratified by home size and profit/nonprofit status. Prescribing data retrieval and analysis are performed by blinded personnel. DISCUSSION: Our study will contribute to an improved understanding of the feasibility and acceptability of a multifaceted intervention aimed at translating knowledge to LTC practitioners. Lessons learned from this study will be valuable in guiding future research and understanding the complexities of translating knowledge in LTC.

Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels.

Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels.

Once-yearly zoledronic acid in older men compared with women with recent hip fracture.

OBJECTIVES: To assess the efficacy of once-yearly zoledronic acid (ZOL) 5 mg in increasing bone mineral density (BMD) in men with a recent hip fracture participating in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once- Yearly Recurrent Fracture Trial and to compare the efficacy with that in women from the same study. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: International multicenter. PARTICIPANTS: Five hundred and eight men and 1,619 women within 90 days of surgical repair of low-trauma hip fracture in the same study (for comparison). INTERVENTION: Once-yearly intravenous (IV) ZOL 5 mg (n = 248) or placebo (n = 260), loading dose of vitamin D, daily calcium, and vitamin D supplements. MEASUREMENT: Changes in BMD. RESULTS: Percentage change from baseline in total hip BMD at Months 12 and 24 was significantly higher with ZOL than with placebo (between-group difference, 2.0%, P = .003, and 3.8%, P = .002, respectively). Percentage change from baseline in femoral neck BMD at Month 24 was significantly higher with ZOL than with placebo (3.8%, P = .003). The BMD benefit was comparable with that observed in women in this study. New clinical fractures occurred in 36 (7.1%) participants (ZOL, n = 16; placebo, n = 20; P = .64). The ZOL safety profile was comparable with that of placebo, with no significant differences in cardiovascular or long-term renal function and a trend toward lower mortality in ZOL-treated men. CONCLUSION: Once-yearly IV ZOL 5 mg increases bone mass at the hip and femoral neck in men within 90 days of repair of a low-trauma hip fracture. Increases were of a similar magnitude to those observed in women in the same study.

A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: no advantage of loading doses over daily supplementation.

BACKGROUND: There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients. The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels. METHODS: In this randomized controlled study, patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario, Canada. Participants were randomized to one of three loading dose groups: placebo; 50,000 IU vitamin D2; or 100,000 IU D2. Following a placebo/loading dose, all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days. Serum 25-hydroxy vitamin D (25-OHD) was measured at baseline, discharge from acute care (approximately 4-weeks), and 3-months. RESULTS: Sixty-five patients were enrolled in the study (44% male). An immediate rise in 25-OHD occurred in the 100,000 group, however there were no significant differences in 25-OHD between the placebo, 50,000 and 100,000 loading dose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15) and 3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09), respectively. At the end of the study, approximately 75% of the placebo and 50,000 groups had reached the target therapeutic range (75 nmol/L), and 44% of the 100,000 group. CONCLUSIONS: In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture, our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2. At the end of the study, all three groups were equally effective in attaining improvement in 25-OHD levels. Given that a daily dose of 1,000 IU vitamin D3 (with or without a loading dose) resulted in at least 25% of patients having suboptimal vitamin D status, patients with acute hip fracture may benefit from a higher daily dose of vitamin D. TRIAL REGISTRATION: Clinical Trials # NCT00424619.

Clinical risk factors for recurrent fracture after hip fracture: a prospective study.

Additional fractures after hip fracture are common, but little is known about the risk factors associated with these events. We determined the clinical risk factors associated with fracture following a low-trauma hip fracture and whether clinical risk factors for subsequent fracture were modified by zoledronic acid (ZOL). In this post hoc analysis of the HORIZON Recurrent Fracture trial, 2,127 men and women were randomized within 90 days of surgical hip fracture repair to receive intravenous ZOL 5 mg yearly or placebo. All patients received a loading dose of vitamin D and daily oral calcium and vitamin D supplements. In the multivariable model age, sex, BMI, femoral neck T score, and one or more fall risk factors were significant predictors of subsequent fracture. Race, history of prior fracture other than the index hip fracture, T score < -2.5 as a dichotomous variable, and type of index hip fracture were not associated with a different risk of subsequent fractures. Treatment with ZOL did not modify the impact of these risk factors. Well-established risk factors for fracture risk such as age, sex, BMI, and fall risk factors will also contribute to fracture risk in patients who have already suffered a hip fracture, while other prior fractures and T score < -2.5 are not predictive of subsequent fractures. Baseline risk factors in hip fracture patients were predictive of fracture in both ZOL- and placebo-treated participants, and there is no difference in the risk of subsequent fractures based on index hip fracture type.

What are the beliefs, attitudes and practices of front-line staff in long-term care (LTC) facilities related to osteoporosis awareness, management and fracture prevention?

BACKGROUND: Compared to the general elderly population, those institutionalized in LTC facilities have the highest prevalence of osteoporosis and subsequently have higher incidences of vertebral and hip fractures. The goal of this study is to determine how well nurses at LTC facilities are educated to properly administer bisphosphonates. A secondary question assessed was the nurse's and PSW's attitudes and beliefs regarding the role and benefits of vitamin D for LTC patients. METHODS: Eight LTC facilities in Hamilton were surveyed, and all nurses were offered a survey. A total 57 registered nurses were surveyed. A 21 item questionnaire was developed to assess existing management practices and specific osteoporosis knowledge areas. RESULTS: The questionnaire assessed the nurse's and personal support worker's (PSWs) education on how to properly administer bisphosphonates by having them select all applicable responses from a list of options. These options included administering the drug before, after or with meals, given with or separate from other medications, given with juice, given with or without water, given with the patient sitting up, or finally given with the patient supine. Only 52% of the nurses and 8.7% of PSWs administered the drug properly, where they selected the options: (given before meals, given with water, given separate from all other medications, and given in a sitting up position). If at least one incorrect option was selected, then it was scored as an inappropriate administration. Bisphosphonates were given before meals by 85% of nurses, given with water by 90%, given separately from other medication by 71%, and was administered in an upright position by 79%. Only 52% of the nurses and 8.7% of PSWs surveyed were administering the drug properly. Regarding the secondary question, of the 57 nurses surveyed, 68% strongly felt their patients should be prescribed vitamin D supplements. Of the 124 PSWs who completed the survey, 44.4% strongly felt their patients should be prescribed vitamin D supplementation. CONCLUSION: Bisphosphonates are quite effective in increasing the bone mineral density of LTC patients, and may reduce fracture rates, but it is only effective if properly administered. In our study, proper administration of bisphosphonate therapy was less than optimal. In summary, although the education of health providers has improved since the mid-1990's, this area still requires further attention and the subject of future quality assurance research.