Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

[Acute geriatric treatment of older trauma patients : Influence on mobility, autonomy and postdischarge destination]. / Geriatrische Komplexbehandlung bei alterstraumatologischen Patienten : Einfluss auf Mobilität, Selbsthilfefähigkeit und Austrittsdestination.

BACKGROUND: Acute geriatric treatment is a type of early rehabilitation for hospitalized seniors to maintain personal autonomy and to avoid nursing home placement. OBJECTIVE: The aim of the study was to describe the changes of mobility and functional independence of older trauma patients during acute geriatric treatment. MATERIAL AND METHODS: This study analyzed admission and discharge assessment data from 164 patients in the geriatric department with fall-related injuries. Mobility and performance in activities of daily living were assessed using the short physical performance battery (SPPB), gait speed and Barthel index. We analyzed changes in mobility from admission to discharge (t-test) and examined differences in mobility between patients returning home and those admitted to long-term care (age-adjusted and gender-adjusted linear regression model). RESULTS: Patients improved their mobility measured by the SPPB by 1.8 points ±â€¯2.1 points, gait speed by 0.10 ±â€¯0.14 m/s and the Barthel index by 13 ±â€¯16 points, all p < 0.001). The number of patients not able to walk decreased from 43% to 14% (p = 0.003). Of the community-dwelling patients 73% were discharged either directly back home or after rehabilitation outside the hospital as a transitional solution. CONCLUSION: In the context of acute geriatric treatment older trauma patients significantly improved their mobility and performance. The majority of patients could return home.

Physical performance among patients aged 70 + in acute care: a preliminar comparison between the Short Physical Performance Battery and the De Morton Mobility Index with regard to sensitivity to change and prediction of discharge destination.

BACKGROUND: The Short Physical Performance Battery (SPPB) and the De Morton Mobility Index (DEMMI) are two commonly used instruments to assess mobility in older patients. AIMS: To compare the two assessments in acute senior trauma patients with regard to sensitivity to change during an acute care, and prediction of discharge destination. METHODS: Medical records were extracted for consecutive trauma patients aged 70 + receiving acute care rehabilitation in the geriatric ward during 9 months. SPPB and DEMMI were obtained at admission and discharge. Sensitivity was analyzed using paired t tests and Cohen's d, and discharge destination with logistic regression predicting the probability of returning home. RESULTS: A total of 69 patients were included in the study [83.7 years (SD 6.3), 78% women, length of stay 10 (IQR 8-10) days]. Overall, SPPB improved from 2.0 (SD 2.5) to 3.8 (SD 2.7; p ≤ 0.001) and DEMMI from 41 (SD 19) to 53 (SD 14; p ≤ 0.001) (Cohen's d: 0.72 for SPPB, 0.62 for DEMMI). Among patients admitted from home each additional point in SPPB at admission and acquired during acute care rehabilitation increased the odds of returning home by 1.7 times (95% CI 1.1-2.8, p = 0.02) and 1.6 times (95% CI 1.1-2.5, p = 0.02). For DEMMI, every 10 points at admission, but not in change, increased the odds of returning home by 2.5 times (95% CI 1.3-5.0, p = 0.007). DISCUSSION AND CONCLUSION: SPPB and DEMMI are both valid mobility assessments for senior patients in acute care. However, SPPB is a better predictor than DEMMI for discharge destination.

[Vitamin D in geriatric patients]. / Vitamin D beim geriatrischen Patienten.

Vitamin D deficiency is widespread in geriatric patients. While vitamin D deficiency is prevalent in about 50% of healthy older adults, the prevalence in geriatric patients with hip fracture increases to over 80%. This is partly due to the fact that sunlight is unreliable as the main source of vitamin D. In addition to insufficient sun intensity from November to April, skin aging plays an important role; it causes a 4-fold reduction in the skin's own vitamin D production during sunshine exposure in older adults compared with younger people. Immobility and institutionalization are additional risk factors for vitamin D deficiency in geriatric patients. At the same time, vitamin D deficiency (< 20 ng/ml) increases parathyroid hormone levels and thus promotes bone loss and the risk of fracture. Severe vitamin D deficiency (< 10 ng/ml) may also lead to reversible muscle weakness resulting in an increased risk of falling. Since falls affect at least every second geriatric patient and hip fractures increase exponentially after the age of 75, the correction of vitamin D deficiency is an important medical and public health effort in these patients. Several randomized intervention trials, comparing 800-1000 IU vitamin D/day versus placebo or calcium, showed a significant reduction in falls and hip fractures in adults ≥65 years of age who had an increased risk of vitamin D deficiency and of falls or fractures. In geriatric patients, implementing vitamin D supplementation at this dosage is currently preferred. A bolus dose of over 24,000 IU/month should be avoided due to the increased risk of falls and fractures. These recommendations remain relevant after a critical review of the four most recent meta-analyses.

Timeline of functional recovery after hip fracture in seniors aged 65 and older: a prospective observational analysis.

We investigated the timeline of functional recovery after hip fracture over 12 months in adults age ≥ 65 years using objective lower extremity function tests and subjective physical functioning. Objective functional recovery was largely complete in the first 6 months, whereas subjective recovery improved up to 9 months after hip fracture. INTRODUCTION: Hip fractures are a major cause of loss of function among seniors. We assessed the timeline of objective and subjective functional recovery after hip fracture. METHODS: We conducted a prospective observational secondary analysis of a 1-year clinical trial on vitamin D and home exercise treatment and complications after hip fracture among 173 patients age ≥ 65 years (mean age 84 years; 79.2% women; 77.4% community-dwelling) conducted from January 2005 through December 2007. Lower extremity function (Timed Up and Go test (TUG), knee extensor and flexor strength) and grip strength was assessed at baseline and at 6 and 12 months follow-up. Subjective physical functioning was assessed using the SF-36 questionnaire also at 3 and 9 months follow-up. Multivariable-adjusted repeated-measures models were used to assess the timeline of functional recovery in the total population and in subgroups of patients. RESULTS: Lower extremity function including TUG (- 61.1%), knee extensor (+ 17.6%), and knee flexor (+ 11.6%) strength improved significantly in the first 6 months (P < 0.001). However, between 6 and 12 months, there was no further significant improvement for any of the functional tests. Grip strength decreased from baseline to 6 months (- 7.9%; P < 0.001) and from 6 to 12 months (- 10.8%; P < 0.001). Subjective physical functioning improved from 3 to 9 months (+ 15.2%, P < 0.001), but no longer thereafter. CONCLUSIONS: Functional recovery after hip fracture may be largely complete in the first 6 months for objective functional tests, whereas may extend up to 9 months for subjective recovery, with oldest-old, female, institutionalized, and cognitively impaired patients recovering most poorly. CLINICAL TRIALS REGISTRY (ORIGINAL TRIAL): NCT00133640.

Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis.

Life expectancy of people living with HIV (PLWH) is reaching similar length as in the general population. Accordingly, age-related comorbidities, including osteoporosis, are increasing. Fracture risk is higher and increases approximately 10 years earlier in PLWH. Classical risk factors of bone fragility are highly prevalent in PLWH but factors specific for HIV infection itself and the type of antiretroviral therapy (ART) (triple combination antiretroviral therapy) regimen (especially tenofovir and protease inhibitors) also contribute to bone loss. The majority of bone loss occurs during virus activity and at initiation of ART (immune reconstitution) and is associated with an increase of bone resorption (upregulation RANKL). Recent data indicate that calcium and vitamin D supplements as ART initiation lower BMD loss. The reduction of tenofovir plasma concentrations with tenofovir alafenamide attenuates BMD loss but it remains unknown whether it will contribute to reduce fracture risk. Hence, special considerations for the management of bone fragility in PLWH are warranted. Based on the current state of epidemiology and pathophysiology of osteoporosis in PLWH, we provide the consensus of the Swiss Association against Osteoporosis on best practice for diagnosis, prevention, and management of osteoporosis in this population. Periodic assessment of fracture risk is indicated in all HIV patients and general preventive measures should be implemented. All postmenopausal women, men above 50 years of age, and patients with other clinical risk for fragility fractures qualify for BMD measurement. An algorithm clarifies when treatment with bisphosphonates and review of ART regimen in favour of more bone-friendly options are indicated.

Influence of fall environment and fall direction on risk of injury among pre-frail and frail adults.

In this prospective study, half of all falls resulted in injury. Pre-frail adults sustained more injuries, while more frail adults had injuries requiring hospitalization or fractures. Pre-frail adults fell more often when in movement compared with frail adults who fell more often when standing and in indoor public spaces. PURPOSE: To assess prospectively how fall environment and direction are related to injury among pre-frail and frail adults. METHODS: We included 200 community-dwelling adults with a prior fall (pre-frail, mean age 77 years) and 173 adults with acute hip fracture (frail, mean age 84 years; 77% community-dwelling). Falls were prospectively recorded using standardized protocols in monthly intervals, including date, time, fall direction and environment, and injury. We used logistic regression to assess the odds of injury adjusting for age, body mass index (BMI), and gender. RESULTS: We recorded 513 falls and 331 fall-related injuries (64.5%) among the 373 participants. While the fall rate was similar between groups, pre-frail adults had more injuries (71% among pre-frail vs. 56% among frail, p = 0.0004) but a lower incidence of major injuries (9% among pre-frail vs. 27% among frail, p = 0.003). Pre-frail adults fell more often while in movement (84% among pre-frail vs. 55% among frail, p < 0.0001), and frail adults fell more often while standing (26% vs. 15% respectively, p = 0.01). The odds of injury among frail adults was increased 3.3-fold when falling sideways (OR = 3.29, 95% CI = 1.68-6.45) and 2.4-fold when falling in an indoor public space (OR = 2.35, 95% CI = 1.00-5.53), and was reduced when falling at home (OR = 0.55, 95% CI = 0.31-0.98). The odds of injury among pre-frail adults was not influenced by environment and was 53% lower when falling backwards (OR = 0.47, 95% CI = 0.26-0.82). CONCLUSION: While pre-frail adults sustain more fall-related injuries, frail adults were more likely to sustain major injuries, especially when falling sideways or outside their home.

Effects of a simple home exercise program and vitamin D supplementation on health-related quality of life after a hip fracture: a randomized controlled trial.

PURPOSE: To test the effects of vitamin D intervention and a simple home exercise program (HE) on health-related quality of life (HRQL) in the first 12 months after hip fracture. METHODS: HRQL was reported in 173 acute hip fracture patients (mean age 84 years, 79% females, 77% community dwelling) who were enrolled in the 12-month 2 × 2 factorial Zurich Hip Fracture Trial. Pre-fracture HRQL was assessed at baseline (4.2 ± 2.2 days post-surgery) and then again at 6 and 12 months after hip fracture surgery by the EuroQol EQ-5D-3L index value (EQ-5D-3L questionnaire). The effects of vitamin D intervention (2000 vs. 800 IU vitamin D3) and exercise (HE vs. no HE) or of the combined interventions on HRQL were assessed using multivariable-adjusted repeated-measures linear mixed-effects regression models. RESULTS: The EQ-5D-3L index value significantly worsened from 0.71 pre-fracture to 0.57 over 12 months, but the degree of worsening did not differ between individual or combined interventions. However, regarding only the late recovery between 6 and 12 months, the group receiving neither intervention (800 IU/day and no HE) experienced a significant further decline in the EQ-5D-3L index value (adjusted mean change = 0.08 [95% CI 0.009, 0.15], p = 0.03) while all other groups remained stable. CONCLUSION: Hip fractures have a long-lasting negative effect on HRQL up to 12 months after hip fracture. However, HE and/or 2000 IU vitamin D per day may help prevent a further decline in HRQL after the first 6 months following the acute hip fracture event.

Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts.

BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. OBJECTIVE: To investigate the association between subclinical thyroid dysfunction and bone loss. METHODS: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. RESULTS: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site. CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

Issues of trial selection and subgroup considerations in the recent meta-analysis of Zhao and colleagues on fracture reduction by calcium and vitamin D supplementation in community-dwelling older adults.

Zhao and colleagues are addressing an important question about the efficacy of calcium and vitamin D on fracture risk reduction among community-dwelling adults age 50+. However, we are concerned about four aspects of their approach, which may affect the validity of their conclusions and implications for public health. INTRODUCTION: We discuss the recent meta-analysis by Zhao and colleagues on the primary prevention of fractures of calcium and vitamin D as well as their combination among community-dwelling adults age 50+. METHODS: Zhao and colleagues included 33 trials that recruited a total of 51,145 community-dwelling participants age 50 years and older, including any randomized clinical trial with a placebo or no treatment in the control group. RESULTS: The authors found no significant association of calcium and/or vitamin D with risk of hip fracture compared with placebo or no treatment and concluded that the routine use of calcium, vitamin D, and the combination in community-dwelling older people is not supported by their findings. We discuss four concerns regarding this meta-analysis, including the target population, the selection of trials with regard to blinding and duration of follow-up, and the lack of adjustment for adherence to the interventions and subgroup analysis by bolus versus daily dosing for vitamin D. CONCLUSION: Based on the four concerns raised in this letter and the fact that there will be a manyfold increase in the data on vitamin D supplementation in community-dwelling senior adults from large ongoing trials, we believe that it is too early to recommend the cessation of vitamin D with or without calcium for the prevention of fractures among community-dwelling adults.

Milk and other dairy foods and risk of hip fracture in men and women.

The role of dairy foods for hip fracture prevention remains controversial. In this study, among US men and women, a glass of milk per day was associated with an 8% lower risk of hip fracture. This contrasts with a reported increased risk with higher milk intake in Swedish women. INTRODUCTION: The purpose of this study was to examine whether higher milk and dairy food consumption are associated with risk of hip fracture in older adults following a report of an increased risk for milk in Swedish women. METHODS: In two US cohorts, 80,600 postmenopausal women and 43,306 men over 50 years of age were followed for up to 32 years. Cox proportional hazards models were used to calculate the relative risks (RR) of hip fracture per daily serving of milk (240 mL) and other dairy foods that were assessed every 4 years, controlling for other dietary intakes, BMI, height, smoking, activity, medications, and disease diagnoses. RESULTS: Two thousand one hundred thirty-eight incident hip fractures were identified in women and 694 in men. Each serving of milk per day was associated with a significant 8% lower risk of hip fracture in men and women combined (RR = 0.92, 95% confidence interval (CI) 0.87 to 0.97). A suggestive inverse association was found for cheese in women only (RR = 0.91, CI 0.81 to 1.02). Yogurt consumption was low and not associated with risk. Total dairy food intake, of which milk contributed about half, was associated with a significant 6% lower risk of hip fracture per daily serving in men and women (RR = 0.94, CI 0.90 to 0.98). Calcium, vitamin D, and protein from non-dairy sources did not modify the association between milk and hip fracture, nor was it explained by contributions of these nutrients from milk. CONCLUSIONS: In this group of older US adults, higher milk consumption was associated with a lower risk of hip fracture.

EULAR/EFORT recommendations for management of patients older than 50†years with a fragility fracture and prevention of subsequent fractures.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.

Gender-specific association between dietary acid load and total lean body mass and its dependency on protein intake in seniors.

Diet-related mild metabolic acidosis may play a role in the development of sarcopenia. We investigated the relationship between dietary acid load and total lean body mass in male and female seniors age ≥ 60 years. We found that a more alkaline diet was associated with a higher %TLM only among senior women. INTRODUCTION: The aim of this study was to determine if dietary acid load is associated with total lean body mass in male and female seniors age ≥ 60 years. METHODS: We investigated 243 seniors (mean age 70.3 ± 6.3; 53% women) age ≥ 60 years who participated in the baseline assessment of a clinical trial on vitamin D treatment and rehabilitation after unilateral knee replacement due to severe knee osteoarthritis. The potential renal acid load (PRAL) was assessed based on individual nutrient intakes derived from a food frequency questionnaire. Body composition including percentage of total lean body mass (%TLM) was determined using dual-energy X-ray absorptiometry. Cross-sectional analyses were performed for men and women separately using multivariable regression models controlling for age, physical activity, smoking status, protein intake (g/kg BW per day), energy intake (kcal), and serum 25-hydroxyvitamin D concentration. We included a pre-defined subgroup analysis by protein intake (< 1 g/kg BW day, > 1 g/kg BW day) and by age group (< 70 years, ≥ 70 years). RESULTS: Adjusted %TLM decreased significantly across PRAL quartiles only among women (P trend = 0.004). Moreover, in subgroup analysis, the negative association between the PRAL and %TLM was most pronounced among women with low protein intake (< 1 g/kg BW per day) and age below 70 years (P = 0.002). Among men, there was no association between the PRAL and %TLM. CONCLUSION: The association between dietary acid load and %TLM seems to be gender-specific, with a negative impact on total lean mass only among senior women. Therefore, an alkaline diet may be beneficial for preserving total lean mass in senior women, especially in those with low protein intake.

Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens.

RATIONALE: Calcidiol can be employed to correct vitamin D deficiency. MAIN RESULTS: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. SIGNIFICANCE: Calcidiol supplementation is effective and safe. INTRODUCTION: The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis. Despite cholecalciferol (vitamin D3) is the most commonly used drug for vitamin D supplementation, the more hydrophilic compound calcidiol (25-hydroxyvitamin D3) can be employed at daily, weekly, and monthly regimens to reach in the short term the target levels of serum 25-hydroxyvitamin D [25(OH)D]. In the administration of different doses of calcidiol pharmacokinetic study (ADDI-D study), the efficacy and safety of daily and weekly dosages of calcidiol were tested. METHODS: A total of 87 Caucasian, community-dwelling, postmenopausal women, aged 55 years or older, with vitamin D inadequacy (serum 25(OH)D levels <30 ng/ml, with mean 25(OH)D below 20 ng/ml, namely 16.5 ± 7.5 ng/ml) were randomized to receive three different dosages of calcidiol: 20 µg/day, 40 µg/day, and 125 µg/week for 3 months. The attained level of serum 25(OH)D was selected as primary endpoint to assess efficacy, while other parameters of mineral metabolism, (serum calcium, parathyroid hormone, phosphate, FGF23, urinary calcium, and markers of bone turnover) were assessed as secondary endpoints to establish safety. RESULTS: In all the three groups, serum 25(OH)D values significantly and promptly rose and plateaued above the 30 ng/ml threshold remaining within safety interval after 14 days of treatment, with similar efficacy for the similar daily and weekly dose regimens. The different dosages were also equally effective in controlling secondary hyperparathyroidism. No significant changes in calcium and phosphate metabolism and in bone turnover markers were observed for any of the treatments, confirming the safety of this compound. CONCLUSIONS: The results of this study demonstrate the short- and mid-term efficacy and safety on core parameters of mineral metabolism of different daily or weekly dosages of calcidiol when used to treat vitamin D inadequacy or deficiency in postmenopausal women. Further studies are needed to assess falls as primary outcome of calcidiol supplementation.

Considerations concerning the definition of sarcopenia.

In this commentary, we describe the sarcopenia spectrum that results in frailty and consider the impact of several components of the frailty definition on its global prevalence. We review proposed operational definitions of sarcopenia and the extent to which they have been shown to predict hard clinical outcomes, such as hip fracture, falls, and mortality. A head-to-head comparison of nine proposed operational definitions of sarcopenia as predictors of falls revealed that the definition involving appendicular lean mass (ALM)/ht2 alone was a significant predictor; the prevalence of sarcopenia by this definition was 11 %. We consider the strengths and limitations of definitions that include functional measurements, such as gait speed and grip strength, along with measures of lean tissue mass. The functional assessments are harder to standardize than the more objective ALM measurements. The prevalence of sarcopenia by definitions that include functional and lean mass measurements tends to be lower than the prevalence by definitions that include lean mass alone. A low prevalence limits opportunity for early identification and application of prevention strategies. For these and other reasons, it seems advantageous to base the operational definition of sarcopenia on ALM/ht2 alone. This commentary addresses the importance of a globally applicable operational definition of sarcopenia and both desirable and undesirable features of such a definition.

Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older.

UNLABELLED: In this study, we compare the extent to which seven available definitions of sarcopenia and two related definitions predict the rate of falling. Our results suggest that the definitions of Baumgartner and Cruz-Jentoft best predict the rate of falls among sarcopenic versus non-sarcopenic community-dwelling seniors. INTRODUCTION: The purpose of the study is to compare the extent to which seven available definitions of sarcopenia and two related definitions predict the prospective rate of falling. METHODS: We studied a cohort of 445 seniors (mean age 71 years, 45 % men) living in the community who were followed with a detailed fall assessment for 3 years. For comparing the rate of falls in sarcopenic versus non-sarcopenic individuals, we used multivariate Poisson regression analyses adjusting for gender and treatment (original intervention tested vitamin D plus calcium against placebo). Of the seven available definitions, three were based on low lean mass alone (Baumgartner, Delmonico 1 and 2) and four required both low muscle mass and decreased performance in a functional test (Fielding, Cruz-Jentoft, Morley, Muscaritoli). The two related definitions were based on low lean mass alone (Studenski 1) and low lean mass contributing to weakness (Studenski 2). RESULTS: Among 445 participants, 231 fell, sustaining 514 falls over the 3-year follow-up. The prospective rate of falls in sarcopenic versus non-sarcopenic individuals was best predicted by the Baumgartner definition based on low lean mass alone (RR = 1.54; 95 % CI 1.09-2.18) with 11 % prevalence of sarcopenia and the Cruz-Jentoft definition based on low lean mass plus decreased functional performance (RR = 1.82; 95 % CI 1.24-2.69) with 7.1 % prevalence of sarcopenia. Consistently, fall rate was non-significantly higher in sarcopenic versus non-sarcopenic individuals based on the definitions of Delmonico 1, Fielding, and Morley. CONCLUSION: Among the definitions investigated, the Baumgartner definition and the Cruz-Jentoft definition had the highest validity for predicting the rate of falls.

Calcifediol versus vitamin D3 effects on gait speed and trunk sway in young postmenopausal women: a double-blind randomized controlled trial.

UNLABELLED: In this double-blind RCT, 4-month treatment with calcifediol compared with vitamin D3 improved gait speed by 18% among young postmenopausal women. Consistently, change in 25(OH)D blood levels over time were significantly correlated with improvement in gait speed in these women. No effect could be demonstrated for trunk sway. INTRODUCTION: The aim of this study is to test the effect of calcifediol compared with vitamin D3 on gait speed and trunk sway. METHODS: Twenty healthy postmenopausal women with an average 25(OH)D level of 13.2 ng/ml (SD = ±3.9) and a mean age of 61.5 years (SD = ±7.2) were randomized to either 20 µg of calcifediol or 20 µg (800 IU) of vitamin D3 per day in a double-blind manner. At baseline and at 4 months of follow-up, the same physiotherapist blinded to treatment allocation tested 8-m gait speed and a body sway test battery (Sway star pitch and roll angle plus velocity while walking 8 m, and standing on both legs on a hard and soft surface). All analyses adjusted for baseline measurement, age, and body mass index. RESULTS: Mean 25(OH)D levels increased to 69.3 ng/ml (SD = ±9.5) in the calcifediol group and to 30.5 ng/ml (SD = ±5.0) in the vitamin D3 group (p < 0.0001). Women receiving calcifediol compared with vitamin D3 had an 18% greater improvement in gait speed at 4-month follow-up (p = 0.046) adjusting for baseline gait speed, age, and body mass index. Also, change in gait speed was significantly correlated with change in serum 25(OH)D concentrations (r = 0.5; p = 0.04). Across three tests of trunk sway, there were no consistent differences between groups and no significant correlation between change in 25(OH)D serum concentrations and change in trunk sway. CONCLUSIONS: Calcifediol improved gait speed in early postmenopausal women compared with vitamin D3 and change in 25(OH)D level was moderately correlated with improvement in gait speed. A benefit on trunk sway could not be demonstrated.

Gender-specific hip fracture risk in community-dwelling and institutionalized seniors age 65 years and older.

UNLABELLED: In this study of acute hip fracture patients, we show that hip fracture rates differ by gender between community-dwelling seniors and seniors residing in nursing homes. While women have a significantly higher rate of hip fracture among the community-dwelling seniors, men have a significantly higher rate among nursing home residents. INTRODUCTION: Differences in gender-specific hip fracture risk between community-dwelling and institutionalized seniors have not been well established, and seasonality of hip fracture risk has been controversial. METHODS: We analyzed detailed data from 1,084 hip fracture patients age 65 years and older admitted to one large hospital center in Zurich, Switzerland. In a sensitivity analysis, we extend to de-personalized data from 1,265 hip fracture patients from the other two large hospital centers in Zurich within the same time frame (total n = 2,349). The denominators were person-times accumulated by the Zurich population in the corresponding age/gender/type of dwelling stratum in each calendar season for the period of the study. RESULTS: In the primary analysis of 1,084 hip fracture patients (mean age 85.1 years; 78% women): Among community-dwelling seniors, the risk of hip fracture was twofold higher among women compared with men (RR = 2.16; 95% CI, 1.74-2.69) independent of age, season, number of comorbidities, and cognitive function; among institutionalized seniors, the risk of hip fracture was 26% lower among women compared with men (RR = 0.77; 95% CI: 0.63-0.95) adjusting for the same confounders. In the sensitivity analysis of 2,349 hip fracture patients (mean age 85.0 years, 76% women), this pattern remained largely unchanged. There is no seasonal swing in hip fracture incidence. CONCLUSION: We confirm for seniors living in the community that women have a higher risk of hip fracture than men. However, among institutionalized seniors, men are at higher risk for hip fracture.

Before and after hip fracture, vitamin D deficiency may not be treated sufficiently.

UNLABELLED: Our findings show that only about 20% of seniors receive vitamin D supplementation prior to their index hip fracture or after the event. We further confirm the high prevalence of severe vitamin D deficiency in this population and show that those who receive supplementation have significantly higher 25-hydroxyvitamin D (25(OH)D) status. INTRODUCTION: The aim of this study is to assess current practice in pre- and post-hip fracture care practice with respect to vitamin D supplementation. METHODS: We surveyed 1,090 acute hip fracture patients age 65 and older admitted to acute care for hip fracture repair; 844 had serum 25-hydroxyvitamin D levels measured upon admission to acute care, and 362 agreed to be followed at 12 month after their hip fracture. Prevalence of vitamin D supplementation was assessed upon admission to acute care (at the time of hip fracture), upon discharge from acute care, and at 6 and 12 months follow-up. RESULTS: Of 1,090 acute hip fracture patients (mean age 85 years, 78% women, 59 % community-dwelling), 19% had received any dose of vitamin D prior to the index hip fracture, 27% (of 854 assessed) at discharge from acute care, 22 % (of 321 assessed) at 6 month, and 21% (of 285 assessed) at 12 month after their hip fracture. At the time of fracture, 45% had 25(OH)D levels below 10 ng/ml, 81% had levels below 20 ng/ml, and 96% had levels below 30 ng/ml. Notably, 25(OH)D levels did not differ by season or gender but were significantly higher among 164 hip fracture patients, with any vitamin D supplementation compared with 680 without supplementation (19.9 versus 10.8 ng/ml; p < 0.0001). CONCLUSION: Only about 20% of seniors receive vitamin D at the time of their fracture and after the event. This is despite the documented 81% prevalence of vitamin D deficiency. Interdisciplinary efforts may be warranted to improve vitamin D supplementation in seniors both before a hip fracture occurs and after.