Women's perspectives regarding osteoporosis, fracture risk, and pharmacologic treatment: a cross-sectional study.

We assessed women's perspectives regarding early preventative therapy for osteoporosis. More than a third of early menopausal women were concerned about bone loss and future fractures, and approximately half were willing to take an intravenous or oral bisphosphonate around the time of menopause to preserve bone health. PURPOSE: Bisphosphonate medications can prevent the substantial bone loss that occurs during early menopause, but little is known about whether women would accept bisphosphonate treatment at this time in their life, when imminent fracture risk is low. We assessed women's perspectives regarding bone loss, fracture risk, and preventative pharmacotherapy in early menopause. METHODS: In this cross-sectional study, Canadian women aged ≥ 45 years were recruited via Facebook advertisement to complete an electronic survey. Primary outcome was the proportion of early menopausal respondents (≤ 5 years since final menstrual period) who were worried about bone loss and fractures. Secondary outcomes were the proportion of early menopausal women willing to accept pharmacologic intervention aimed at preventing either bone loss or future fractures. We compared responses between early menopausal women and older women (> 5 years since final menstrual period). RESULTS: 2033 women responded to the Facebook advertisement, 1195 eligible women (aged: 45 to 89 years) started the survey, and 966 completed it. Among early menopausal respondents (N = 98), 38 (42%) were worried about future fractures and 9 of 25 (36%) who had a prior bone mineral density scan were worried about their results. A total of 42 (47%) were willing to start medication to prevent fractures, and 48 (54%) would start medication to prevent bone loss. Responses were comparable between early menopausal women and older women. CONCLUSION: Menopausal women are concerned about bone loss and fractures. Many women would consider early menopausal pharmacotherapy, with the goals of preserving bone health and lowering their risk of fractures.

Comparison of Bone Quality Among Winter Endurance Athletes with and Without Risk Factors for Relative Energy Deficiency in Sport (REDs): A Cross-Sectional Study.

Relative Energy Deficiency in Sport (REDs) is a syndrome describing the relationship between prolonged and/or severe low energy availability and negative health and performance outcomes. The high energy expenditures incurred during training and competition put endurance athletes at risk of REDs. The objective of this study was to investigate differences in bone quality in winter endurance athletes classified as either low-risk versus at-risk for REDs. Forty-four participants were recruited (M = 18; F = 26). Bone quality was assessed at the distal radius and tibia using high resolution peripheral quantitative computed tomography (HR-pQCT), and at the hip and spine using dual X-ray absorptiometry (DXA). Finite element analysis was used to estimate bone strength. Participants were grouped using modified criteria from the REDs Clinical Assessment Tool Version 1. Fourteen participants (M = 3; F = 11), were classified as at-risk of REDs (≥ 3 risk factors). Measured with HR-pQCT, cortical bone area (radius) and bone strength (radius and tibia) were 6.8%, 13.1% and 10.3% lower (p = 0.025, p = 0.033, p = 0.027) respectively, in at-risk compared with low-risk participants. Using DXA, femoral neck areal bone density was 9.4% lower in at-risk compared with low-risk participants (p = 0.005). At-risk male participants had 21.9% lower femoral neck areal bone density (via DXA) than low-risk males (p = 0.020) with no significant differences in females. Overall, 33.3% of athletes were at-risk for REDs and had lower bone quality than those at low-risk.

Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss.

In a 36-month randomized controlled trial examining the effect of high-dose vitamin D3 on radial and tibial total bone mineral density (TtBMD), measured by high-resolution peripheral quantitative tomography (HR-pQCT), participants (311 healthy males and females aged 55-70 years with dual-energy X-ray absorptiometry T-scores > -2.5 without vitamin D deficiency) were randomized to receive 400 IU (N = 109), 4000 IU (N = 100), or 10,000 IU (N = 102) daily. Participants had HR-pQCT radius and tibia scans and blood sampling at baseline, 6, 12, 24, and 36 months. This secondary analysis examined the effect of vitamin D dose on plasma measurements of the vitamin D metabolome by liquid chromatography-tandem mass spectrometry (LC-MS/MS), exploring whether the observed decline in TtBMD was associated with changes in four key metabolites [25-(OH)D3 ; 24,25-(OH)2 D3 ; 1,25-(OH)2 D3 ; and 1,24,25-(OH)3 D3 ]. The relationship between peak values in vitamin D metabolites and changes in TtBMD over 36 months was assessed using linear regression, controlling for sex. Increasing vitamin D dose was associated with a marked increase in 25-(OH)D3 , 24,25-(OH)2 D3 and 1,24,25-(OH)3 D3 , but no dose-related change in plasma 1,25-(OH)2 D3 was observed. There was a significant negative slope for radius TtBMD and 1,24,25-(OH)3 D3 (-0.05, 95% confidence interval [CI] -0.08, -0.03, p < 0.001) after controlling for sex. A significant interaction between TtBMD and sex was seen for 25-(OH)D3 (female: -0.01, 95% CI -0.12, -0.07; male: -0.04, 95% CI -0.06, -0.01, p = 0.001) and 24,25-(OH)2 D3 (female: -0.75, 95% CI -0.98, -0.52; male: -0.35, 95% CI -0.59, -0.11, p < 0.001). For the tibia there was a significant negative slope for 25-(OH)D3 (-0.03, 95% CI -0.05, -0.01, p < 0.001), 24,25-(OH)2 D3 (-0.30, 95% CI -0.44, -0.16, p < 0.001), and 1,24,25-(OH)3 D3 (-0.03, 95% CI -0.05, -0.01, p = 0.01) after controlling for sex. These results suggest vitamin D metabolites other than 1,25-(OH)2 D3 may be responsible for the bone loss seen in the Calgary Vitamin D Study. Although plasma 1,25-(OH)2 D3 did not change with vitamin D dose, it is possible rapid catabolism to 1,24,25-(OH)3 D3 prevented the detection of a dose-related rise in plasma 1,25-(OH)2 D3 . © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Trials.

Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the time of menopause, might prevent excessive bone loss and lower long-term fracture risk. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effects of nitrogen-containing bisphosphonates on fracture incidence, bone mineral density (BMD), and bone turnover markers in early menopausal women (ie, perimenopausal or <5 years postmenopausal) over ≥12 months. Medline, Embase, CENTRAL, and CINAHL were searched in July 2022. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Random effect meta-analysis was undertaken using RevMan v5.3. In total, 12 trials were included (n = 1722 women); five evaluated alendronate, three risedronate, three ibandronate, and one zoledronate. Four were at low risk of bias; eight raised some concerns. Fractures were infrequent in the three studies that reported them. Compared with placebo, bisphosphonates improved BMD over 12 months (mean percentage difference, 95% confidence interval [CI]) at the spine (4.32%, 95% CI, 3.10%-5.54%, p < 0.0001, n = 8 studies), the femoral neck (2.56%, 95% CI, 1.85%-3.27%, p = 0.001, n = 6 studies), and the total hip (1.22%, 95% CI 0.16%-2.28%, p = 0.002, n = 4 studies). Over treatment durations of 24 to 72 months, bisphosphonates improved BMD at the spine (5.81%, 95% CI 4.71%-6.91%, p < 0.0001, n = 8 studies), femoral neck (3.89%, 95% CI 2.73%-5.05%, p = 0.0001, n = 5 studies) and total hip (4.09%, 95% CI 2.81%-5.37%, p < 0.0001, n = 4 studies). Bisphosphonates reduced urinary N-telopeptide (-52.2%, 95% CI -60.3% to -44.2%, p < 0.00001, n = 3 studies) and bone-specific alkaline phosphatase (-34.2%, 95% CI -42.6% to -25.8%, p < 0.00001, n = 4 studies) more than placebo at 12 months. This systematic review and meta-analysis shows that bisphosphonates improve BMD and lower bone turnover markers in early menopause, warranting further investigation of these agents for osteoporosis prevention. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Effects of probiotics on bone mineral density and bone turnover: A systematic review.

Probiotic supplements have been shown to improve bone health in animal models, although it remains uncertain whether these beneficial effects extend to humans. We undertook a systematic review of the literature to determine the effects of probiotic interventions on skeletal outcomes in postmenopausal women. MEDLINE, EMBASE, CENTRAL, and the Cochrane Database of Systematic Reviews were searched from inception to October 2020 for controlled trials comparing the effects of probiotic-containing supplements with placebo on bone mineral density (BMD) or bone turnover markers. Risk of bias was assessed using the Cochrane Risk of Bias 2 Tool. Of 338 records identified, six randomized, placebo-controlled trials (n = 632) were eligible for inclusion. All studies assessed postmenopausal women for durations of 6-12 months; three were considered to be at high risk of bias. Four studies examined Lactobacillus-containing probiotics, one assessed a proprietary blend of lactic acid bacteria, and one evaluated Bacillus subtilis. Effects of probiotic interventions on BMD were inconsistent, with the majority of studies demonstrating no benefit at the spine or hip. Probiotic effects on bone turnover markers were similarly heterogeneous. High quality studies are needed to determine whether probiotic interventions have a role in maintaining bone health in humans.

Response to High-Dose Vitamin D Supplementation Is Specific to Imaging Modality and Skeletal Site.

High-dose vitamin D supplementation (4000 or 10,000 IU/d) in vitamin D-sufficient individuals results in a dose-dependent decrease in radius and tibia total bone mineral density (Tt.BMD) compared with 400 IU/d. This exploratory analysis examined whether the response to high-dose vitamin D supplementation depends on imaging modality and skeletal site. Participants were aged 55 to 70 years, not osteoporotic, with serum 25(OH)D 30 to 125 nM. Participants' radius and tibia were scanned on high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure Tt.BMD, trabecular bone volume fraction (Tb.BV/TV), trabecular separation (Tb.Sp), cortical thickness (Ct.Th), and finite element analysis (FEA) estimated failure load. Three-dimensional image registration was used. Dual-energy X-ray absorptiometry (DXA) scans of the hip, spine, and radius measured areal BMD (aBMD) and trabecular bone score (TBS). Constrained linear mixed-effects models determined treatment group-by-time and treatment group-by-time-by-sex interactions. The treatment group-by-time interaction previously observed for radial Tt.BMD was observed at both ultradistal (UD, p < 0.001) and 33% (p < 0.001) aBMD sites. However, the treatment group-by-time-by-sex interaction observed for radial Tt.BMD was not observed with aBMD at either the UD or 33% site, and the 4000 and 400 groups did not differ. Registered radial FEA results mirrored Tt.BMD. An increase in Tb.Sp and decrease in Ct.Th underpinned dose-dependent changes in radial BMD and strength. We observed no effects in DXA-based aBMD at the hip or spine or TBS. At the tibia, we observed a time-by-treatment group effect for Tb.BV/TV. Given that DXA measures at the radius did not detect sex differences or differences between the 4000 and 400 groups, HR-pQCT at the radius may be more sensitive for examining bone changes after vitamin D supplementation. Although DXA did not reveal treatment effects at the hip or spine, whether that is a true skeletal site difference or a lack of modality sensitivity remains unclear. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A retrospective review of the community medicine needs from osteoporosis services in Canada.

BACKGROUND: Comprehensive, real-world osteoporosis care has many facets not explicitly addressed in practice guidelines. We sought to determine the areas of knowledge and practice needs in osteoporosis medicine for the purpose of developing an osteoporosis curriculum for specialist trainees and knowledge translation tools for primary care. METHODS: This was a retrospective review of referral questions received from primary care and specialists to an academic, multi-disciplinary tertiary osteoporosis and metabolic bone clinic. There were 400 referrals in each of 5 years (2015-2019) selected randomly for review. The primary referral question was elucidated and assigned to one of 16 pre-determined referral topics reflecting questions in the care of osteoporosis and metabolic bone patients. The top 7 referral topics by frequency were determined while recording the referral source. RESULTS: The majority of referrals (71%) came from urban primary care. The most common specialists to request care included rheumatology, oncology, gastroenterology and orthopedic surgery (fracture liaison services). Primary care referrals predominantly requested assistance with routine osteoporosis assessments, bisphosphonate holidays, bisphosphonate adverse effects/alternatives, fractures occurring despite therapy and adverse changes on bone densitometry despite treatment. Specialists most often referred patients with complex secondary bone diseases or cancer. The main study limitation was that knowledge needs of referring physicians were inferred from the referral question rather than tested directly. CONCLUSION: By assessing actual community demand for services, this study identified several such topics that may be useful targets to develop high quality knowledge translation tools and curriculum design in programs training specialists in osteoporosis care.

Drug therapy for osteoporosis in older adults.

The goal of osteoporosis management is to prevent fractures. Several pharmacological agents are available to lower fracture risk, either by reducing bone resorption or by stimulating bone formation. Bisphosphonates are the most widely used anti-resorptives, reducing bone turnover markers to low premenopausal concentrations and reducing fracture rates (vertebral by 50-70%, non-vertebral by 20-30%, and hip by ~40%). Bisphosphonates bind avidly to bone mineral and have an offset of effect measured in months to years. Long term, continuous use of oral bisphosphonates is usually interspersed with drug holidays of 1-2 years, to minimise the risk of atypical femoral fractures. Denosumab is a monoclonal antibody against RANKL that potently inhibits osteoclast development and activity. Denosumab is administered by subcutaneous injection every 6 months. Anti-fracture effects of denosumab are similar to those of the bisphosphonates, but there is a pronounced loss of anti-resorptive effect from 7 months after the last injection, which can result in clusters of rebound vertebral fractures. Two classes of anabolic drugs are now available to stimulate bone formation. Teriparatide and abaloparatide both target the parathyroid hormone-1 receptor, and are given by daily subcutaneous injection for up to 2 years. Romosozumab is an anti-sclerostin monoclonal antibody that stimulates bone formation and inhibits resorption. Romosozumab is given as monthly subcutaneous injections for 1 year. Head-to-head studies suggest that anabolic agents have greater anti-fracture efficacy and produce larger increases in bone density than anti-resorptive drugs. The effects of anabolic agents are transient, so transition to anti-resorptive drugs is required. The optimal strategy for cycling anabolics, anti-resorptives, and off-treatment periods remains to be determined.

Comparison of 2 fracture risk estimation processes in Alberta: a cross-sectional chart review.

BACKGROUND: In Canada, decisions regarding osteoporosis pharmacotherapy are based on estimated 10-year risk of osteoporotic fracture. We aimed to determine how frequently 2 common approaches (Canadian Association of Radiologists and Osteoporosis Canada [CAROC] tool and Fracture Risk Assessment Tool [FRAX]) produced different estimates and to seek possible explanations for differences. METHODS: We conducted a cross-sectional chart review at a tertiary osteoporosis centre (Dr. David Hanley Osteoporosis Centre in Calgary). Included patients were women referred for consideration of osteoporosis pharmacotherapy who attended a consultation between 2016 and 2019 and whose charts contained 10-year osteoporotic fracture risk estimates using both the CAROC tool (based on bone mineral density [BMD] results) and FRAX (based on BMD results and clinically assessed fracture risk factors). Risk estimates provided on BMD reports (calculated with CAROC) and generated through osteoporosis clinic consultation (calculated with FRAX, including BMD) were categorized as low (< 10.0%), moderate (10.0%-19.9%) or high (≥ 20.0%). Estimates were considered discordant when they placed the patient in different risk categories. RESULTS: Of 190 patients evaluated, 99 (52.1%) had discordant risk estimates. Although a similar proportion were considered high risk by BMD reports using the CAROC tool (17.9%) and clinic charts using FRAX (19.5%), the 2 methods identified different patients as being high risk. Around the crucial high-risk (20.0%) treatment threshold, discordance was present in 37 patients (19.5%, 95% confidence interval [CI] 14.5%-25.7%); discordance around the moderate-risk (10.0%) threshold was present in 69 (36.3%, 95% CI 29.5%-43.2%) patients. Disagreement regarding fracture history between BMD reports and clinic charts was observed in 19.8% of patients. INTERPRETATION: Fracture risk estimates on BMD reports (using the CAROC tool) and those calculated in the clinical setting (using FRAX) frequently result in different risk classification. Osteoporosis treatment decisions may differ in up to half of patients depending on which estimate is used, highlighting the need for a consistent and accurate assessment process for fracture risk.

Group medical consultation for osteoporosis: a prospective pilot study of patient experience in Canadian tertiary care.

BACKGROUND: Delivery of patient-centred care is limited by physician time. Group medical consultations may save physician time without compromising patient experience. AIM: To assess patient experience and specialist physician time commitment in a group consultation for osteoporosis. DESIGN AND SETTING: Prospective pilot study at a tertiary osteoporosis centre in Canada between May 2016 and June 2019. METHOD: The authors evaluated women referred for osteoporosis who chose a 2-hour group consultation instead of a one-to-one consultation. Group consultations were led by an osteoporosis nurse and specialist physician, and consisted of individualised fracture risk assessment and education regarding osteoporosis therapies, followed by a decision-making exercise to choose a treatment plan. Patients then followed up with their GPs to implement this plan. Patient experience was assessed via a questionnaire immediately and 3 months post-consultation, at which time GP satisfaction and patient treatment status were also surveyed. RESULTS: Of 560 referrals received, 18 patients declined osteoporosis specialist assessment, 54 could not be contacted, 303 attended a one-to- one consultation, and 185 attended a group consultation. Mean participant age was 62.8 years (standard deviation [SD] 5.8) and the Fracture Risk Assessment Tool (FRAX) 10-year osteoporotic fracture risk was 13.0 (SD 7.0)%. Immediately post-consultation, 104 (97.2%) patients were satisfied and 102 (95.3%) felt included in decision making. Satisfaction was reported by 95/99 (96.0%) patients and 27/36 (75.0%) GPs. Treatment plans had been enacted by 90 (90.1%) patients. For a matched number of individual consultations, each group session conferred a specialist physician time savings of 5.5 hours. CONCLUSION: Group consultations represent a satisfactory and time-efficient alternative to one-to-one consultations for select patients with osteoporosis.

Autonomy begets adherence: decisions to start and persist with osteoporosis treatment after group medical consultation.

Many individuals prescribed osteoporosis pharmacotherapy either do not start or do not persist with treatment. In this study, women who attended a group medical visit at an osteoporosis center which involved fracture risk assessment and focused on autonomous decision-making made treatment decisions with high confidence. Those who started pharmacotherapy were highly persistent. PURPOSE: Adherence and persistence with osteoporosis pharmacotherapy is low, possibly reflecting lack of confidence in physicians' treatment recommendations. We evaluated treatment decisions, decisional confidence, and 12-month treatment adherence among women who attended a group bone health consultation that fostered autonomous decision-making. METHODS: We prospectively assessed postmenopausal women referred to an osteoporosis clinic who chose to attend a group medical visit in lieu of one-on-one consultation. The group visit was facilitated by a specialist physician and nurse, involving estimation of 10-year major osteoporotic fracture risk (using FRAX®) and extensive education regarding fracture consequences and potential advantages and disadvantages of pharmacotherapy. No direct advice was given by the specialist. Post-consult, participants made an autonomous decision regarding treatment intent and followed up with their family physician to enact their chosen plan. Intentions to initiate pharmacotherapy were assessed immediately post-consult. Treatment status and decisional confidence were evaluated 3 and 12 months later. Three-month treatment status was considered to reflect final treatment decision. Persistence was defined as proportion of participants on treatment at 3 months who remained treated at 12 months. RESULTS: One hundred one women (mean (SD) age, 62.7 years (5.8); median (IQR) FRAX®, 10.7% (8.3-17.6)) participated. Immediately post-consult, 27 (26.7%) intended to initiate treatment. At 3 months, 23 (22.8%) were treated, and at 12 months, 21 (91.3%) remained persistent. Of 89 questionnaire respondents at 12 months, 85 (95.5%) reported confidence in their treatment decision. CONCLUSION: When postmenopausal women are provided with individualized fracture risk estimates and enabled to make autonomous decisions regarding pharmacotherapy, ultimate decisions to receive treatment are made with confidence and result in high persistence at 12 months.

Adverse Effects of High-Dose Vitamin D Supplementation on Volumetric Bone Density Are Greater in Females than Males.

Three years of high-dose vitamin D supplementation (400 IU, 4000 IU, 10,000 IU) in healthy vitamin D-sufficient individuals aged 55 to 70 years (serum 25(OH)D 30-125 nmol/L at baseline), resulted in a negative dose-response relationship for bone density and strength. This study examined whether response differed between males and females. A total of 311 participants (53% male) were randomized to 400 IU (male = 61, female = 48), 4000 IU (male = 51, female = 49), or 10,000 IU (male = 53, female = 49) daily vitamin D3 . Participants were scanned with high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure total volumetric BMD (TtBMD) at baseline, 6, 12, 24, and 36 months. Finite element analysis estimated bone strength. Balance, physical function, and clinical biochemistry parameters were also assessed. Constrained linear mixed effects models determined time-by-treatment group-by-sex interactions. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L (400 IU); 81.3, 115.3, and 132.2 (4000 IU); and 78.4, 188.0, and 144.4 (10,000 IU), respectively. There were significant time-by-treatment group-by-sex interactions for TtBMD at the radius (p = .002) and tibia (p = .005). Treatment with 4000 IU or 10,000 IU compared to 400 IU resulted in TtBMD losses in females, but this was not observed with males. After 3 years, females lost 1.8% (400 IU), 3.8% (4000 IU), and 5.5% (10,000 IU), whereas males lost 0.9% (400 IU), 1.3% (4000 IU), and 1.9% (10,000 IU) at the radius. At the tibia, losses in TtBMD were smaller, but followed a similar trend. There were no significant bone strength interactions. Vitamin D supplementation with 4000 IU or 10,000 IU, compared with 400 IU daily, resulted in greater losses of TtBMD over 3 years in healthy vitamin D-sufficient females, but not males. These results are clinically relevant, because vitamin D supplementation is widely administered to postmenopausal females for osteoporosis prevention. Our findings do not support a benefit of high-dose vitamin D supplementation for bone health, and raise the possibility of harm for females. © 2020 American Society for Bone and Mineral Research (ASBMR).

Benefits of Bisphosphonate Therapy: Beyond the Skeleton.

PURPOSE OF REVIEW: Recent evidence from clinical trials and observational studies raises the possibility that bisphosphonate use might confer a lower risk of cardiovascular disease and cancer, resulting in a mortality benefit. This review summarizes clinical and preclinical studies examining the non-skeletal effects of bisphosphonates. RECENT FINDINGS: Data from clinical trials are conflicting regarding whether or not bisphosphonates have beneficial effects on mortality, cardiovascular events, or cancer incidence. No clinical trials have assessed these outcomes as primary endpoints, and most trials were shorter than 4 years. Observational data suggest that bisphosphonate users may have lower mortality, delayed progression of vascular calcification and atherosclerotic burden, and reduced incidence of breast and colorectal cancer compared to non-users. Preclinical studies confirm that bisphosphonates can be taken up by macrophages and monocytes, and nitrogen-containing bisphosphonates have the ability to disrupt the mevalonate pathway within these cells. In this manner, bisphosphonates exert anti-atherogenic and anti-cancer effects. Bisphosphonates also appear to exert protective effects on vascular smooth muscle cells and endothelial cells and may have direct cytotoxic effects on cancer cells. The balance of evidence does not support bisphosphonate treatment for the primary purpose of improving non-skeletal outcomes, although appropriately designed controlled trials that further explore this possibility are both justified and required. Patients with skeletal indications for bisphosphonate therapy can be reassured that these agents are not associated with increased mortality, cardiovascular disease, or cancer incidence.

Postural Balance Effects Associated with 400, 4000 or 10,000 IU Vitamin D3 Daily for Three Years: A Secondary Analysis of a Randomized Clinical Trial.

Vitamin D supplementation is proposed as a fall prevention strategy, as it may improve neuromuscular function. We examined whether three years of vitamin D supplementation (400, 4000 or 10,000 IU daily) affects postural sway in older adults. Three hundred and seventy-three non-osteoporotic, vitamin D-sufficient, community-dwelling healthy adults, aged 55-70 years, were randomized to 400 (n = 124), 4000 (n = 125) or 10,000 (n = 124) IU daily vitamin D3 for three years. Sway index was assessed at baseline, 12-, 24- and 36-months using the Biosway machine. We tested participants under four conditions: eyes open or eyes closed with firm (EOFI, ECFI) or foam (EOFO, ECFO) surfaces. Secondary assessments examined sway in the anterior-posterior (AP) and medio-lateral (ML) directions. Linear mixed effects models compared sway between supplementation groups across time. Postural sway under EOFO and ECFO conditions significantly improved in all supplementation groups over time. Postural sway did not differ between supplementation groups at any time under any testing conditions in normal, AP or ML directions (p > 0.05 for all). Our findings suggest that high dose (4000 or 10,000 IU) vitamin D supplementation neither benefit nor impair balance compared with 400 IU daily in non-osteoporotic, vitamin D-sufficient, healthy older adults.

At Odds About the Odds: Women's Choices to Accept Osteoporosis Medications Do Not Closely Agree with Physician-Set Treatment Thresholds.

BACKGROUND: Osteoporosis guidelines recommend pharmacologic therapy based on 10-year risk of major osteoporotic fracture (MOF) and hip fracture, which may fail to account for patient-specific experiences and values. OBJECTIVE: We aimed to determine whether patient decisions to initiate osteoporosis medication agree with guideline-recommended intervention thresholds. DESIGN AND PARTICIPANTS: This prospective cohort study included women aged ≥ 45 with age-associated osteoporosis who attended a group osteoporosis self-management consultation at a tertiary osteoporosis center. INTERVENTION: A group osteoporosis self-management consultation, during which participants received osteoporosis education and then calculated1 their 10-year MOF and hip fracture risk using FRAX and2 their predicted absolute fracture risk with therapy (assuming 40% relative reduction). Participants then made autonomous decisions regarding treatment initiation. MAIN MEASURES: We evaluated agreement between treatment decisions and physician-set intervention thresholds (10-year MOF risk ≥ 20%, hip fracture risk ≥ 3%). KEY RESULTS: Among 85 women (median [IQR] age 62 [58-67]), 27% accepted treatment (median [IQR] MOF risk, 15.1% [9.9-22.0]; hip fracture risk, 3.3% [1.3-5.3]), 46% declined (MOF risk, 9.5% [6.5-11.6]; hip fracture risk, 1.8% [0.6-2.3]), and 27% remained undecided (MOF risk, 14.0% [9.8-20.2]; hip fracture risk, 4.4% [1.7-4.9]). There was wide overlap in fracture risk between treatment acceptors and non-acceptors. Odds of accepting treatment were higher in women with prior fragility fracture (50% accepted; OR, 5.3; 95% CI, 1.9-15.2; p = 0.0015) and with hip fracture risk ≥ 3% (32% accepted; OR, 3.6; 95% CI, 1.4-9.2; p = 0.012), but not MOF risk ≥ 20% (47% accepted; OR, 3.0; 95% CI, 1.0-8.5; p = 0.105). CONCLUSIONS: Informed decisions to start osteoporosis treatment are highly personal and not easily predicted using fracture risk. Guideline-recommended intervention thresholds may not permit sufficient consideration of patient preferences.

Safety of High-Dose Vitamin D Supplementation: Secondary Analysis of a Randomized Controlled Trial.

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, 4 000, 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.