Adherence to the MIND diet and the odds of mild cognitive impairment in generally healthy older adults: The 3-year DO-HEALTH study.

BACKGROUND: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may slow cognitive decline in older adults. A potential mechanism could be possible anti-inflammatory properties of the MIND-diet. OBJECTIVE: To examine whether adherence to the MIND diet at baseline is associated with the odds of mild cognitive impairment (MCI) and changes in biomarkers of inflammation (High-sensitivity C-reactive Protein(hsCRP), interleukin-6(IL-6)) over three years in adults ≥70 years. METHODS: Adherence to the MIND diet was assessed by food frequency questionnaire (FFQ) at baseline and after three years. Presence of MCI based on the Montreal Cognitive Assessment (MoCA) was defined as <26 (MCI26), or <24 (MCI24). We performed a minimally adjusted model controlling for sex, prior fall, linear spline at age 85, time, treatment and study site. The fully adjusted model also adjusted for education, BMI, physical activity, depression score, daily energy intake, and comorbidity score. To assess the change in inflammatory markers from baseline, we used linear-mixed-effect models adjusted for the same variables plus the respective baseline concentrations. Sensitivity analyses accounting for practice effects of repeated cognitive tests using the reliable change index for both MoCA cut-offs were done. RESULTS: We included 2028 of 2157 DO-HEALTH participants (60.5% women; mean age 74.88 years) with complete data. Adherence to the MIND diet at baseline was not associated with cognitive decline over three years, neither at MoCA < 26 (OR (95%CI) = 0.99 (0.94-1.04)) nor at MoCA < 24 (OR (95%CI) = 1.03 (0.96-1.1)). Applying the reliable change index to the two cut-offs confirmed the findings. Further, the MIND diet adherence was not associated with the change in MoCA score from baseline in DO-HEALTH. For inflammatory biomarkers MIND-diet baseline adherence was not associated with changes in hsCRP or IL-6. CONCLUSION: Adherence to the MIND-diet was neither associated with the odds of MCI, nor with hsCRP or IL-6 at baseline. Moreover, change in MIND-diet over three years was not associated with changes in hsCRP or IL-6.

Effect of vitamin D supplementation on circulating fibroblast growth factor-23 concentration in adults with prediabetes.

BACKGROUND: Recent meta-analyses report that vitamin D supplementation increases blood fibroblast growth factor-23 (FGF23) level. OBJECTIVES: To determine the effect of 4000 IU/day of vitamin D3 for 12 months on circulating FGF23 levels. We also examined the association of the achieved 25-hydroxyvitamin D level [25(OH)D] with the FGF23 level at 12 months and with 12-month changes in FGF23. METHODS: An ancillary analysis among adults 70 years and older with prediabetes who participated in a trial comparing vitamin D3 4000 IU/day with placebo. Plasma intact FGF23 and serum 25(OH)D were measured at baseline and month 12 (M12). RESULTS: Characteristics of the 52 participants (vitamin D3 n = 28; placebo n = 24) did not differ significantly aside from more women than men in the vitamin D3 group. Mean ± SD age was 73.8 ± 3.7 years, BMI 31.3 ± 4.2 kg/m2, and glomerular filtration rate (GFR) 76.3 ± 11.8 mL/min/1.73m2 Baseline serum 25(OH)D level was 33.4 ± 10.8 ng/mL and increased at M12 to 54.9 ± 14.8 ng/mL in the vitamin D3 group versus 33.4 ± 14.9 in the placebo (p < 0.001). At baseline, GFR was inversely associated with FGF23 (r = - 0.349, p = 0.011). Change in FGF23 level at M12 did not differ significantly between vitamin D3 and placebo. In all participants combined, the achieved serum 25(OH)D level at M12 was not significantly associated with the M12 plasma FGF23 or the M12 change in FGF23. CONCLUSION: In obese older adults with sufficient vitamin D status and normal renal function, vitamin D3 4000 IU/day for 12 months did not significantly alter plasma intact FGF23 levels. CLINICALTRIALS: gov NCT 01,942,694, registered 9/16/2013.

Vitamin D in the older population: a consensus statement.

BACKGROUND: This paper reports results from the 5th International Conference "Controversies in Vitamin D" that was held in Stresa, Italy, 15-18 September 2021. The conference is part of this series that started in 2017 and has been conducted annually since. The objective of these conferences is to identify timely and controversial topics related to Vitamin D. Dissemination of the results of the conference through publications in peer-reviewed journals is an important means by which the most up to date information can be shared with physicians, investigators, and other health care professionals. Vitamin D and aging, the subject of this paper was featured at the conference. METHODS: Participants were selected to review available literature on assigned topics related to vitamin D and aging and to present their findings with illustrative material, the intent of which was to stimulate discussion and to arrive at a consensus. The presentations were directed towards the following areas: impact of aging on vitamin D production and levels; skeletal effects of vitamin D deficiency in the older population; falls and vitamin D in the aging; potential extra skeletal effects of vitamin D; and strategies to prevent vitamin D deficiency. A final topic was related to how vitamin D might influence the efficacy of vaccines for Covid-19. RESULTS: Hypovitaminosis D can lead to several skeletal and extra-skeletal outcomes. Older adults are at risk for vitamin D deficiency as both production and metabolism of vitamin D change with aging due to factors, such as reduced sun exposure and reduced production capacity of the skin. Skeletal consequences of these age-related changes can include reduced bone mineral density, osteomalacia and fractures. Potential extra-skeletal effects can include added risks for falls, reduced muscle strength, diabetes, cancer, and cardiovascular disease. Strategies to avoid these vitamin D deficiency-related negative outcomes include sun exposure, food fortification, and supplementation. While aging does not diminish sufficient reserve capacity for cutaneous vitamin D production, concerns about skin cancers and practical matters for the institutionalized elderly limit this option. Supplementation with vitamin D is the best option either pharmacologically or through food fortification. Regardless of treatment strategies, interventions to restore sufficient vitamin D status will show positive results only in those who are truly deficient. Thus, treatment goals should focus on avoiding 25(OH)D serum levels <30 nmol/l, with a goal to reach levels >50 nmol/l. CONCLUSIONS: The results of this conference has led to consensus on several issues. Vitamin D supplementation should be combined with calcium to reduce fractures in the older population. The goal for adequate Vitamin D status should be to reach a serum level of 25(OH)D >50 nmol/l. It appears that daily low-dose vitamin D regimens reduce the risk of falling, especially in the elderly, compared with infrequent, large bolus doses that may increase it. The role of Vitamin D supplementation on muscle strength remains to be clarified. On the other hand, supplementation decreases the risk of progression to T2D from prediabetes among those who are Vitamin Ddeficient. Of three possible strategies to establish vitamin D sufficiency - sunshine exposure, food fortification, and supplementation - the latter seems to be the most effective and practical in the aging population.

Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial.

Objective: The aim of this study was to test the individual and combined benefit of vitamin D, omega-3, and a simple home strength exercise program on the risk of any invasive cancer. Design: The DO-HEALTH trial is a three-year, multicenter, 2 × 2 × 2 factorial design double-blind, randomized-controlled trial to test the individual and combined benefit of three public health interventions. Setting: The trial was conducted between December 2012 and December 2017 in five European countries. Participants: Generally healthy community-dwelling adults ≥70 years were recruited. Interventions: Supplemental 2000 IU/day of vitamin D3, and/or 1 g/day of marine omega-3s, and/or a simple home strength exercise (SHEP) programme compared to placebo and control exercise. Main outcome: In this pre-defined exploratory analysis, time-to-development of any verified invasive cancer was the primary outcome in an adjusted, intent-to-treat analysis. Results: In total, 2,157 participants (mean age 74.9 years; 61.7% women; 40.7% with 25-OH vitamin D below 20 /ml, 83% at least moderately physically active) were randomized. Over a median follow-up of 2.99 years, 81 invasive cancer cases were diagnosed and verified. For the three individual treatments, the adjusted hazard ratios (HRs, 95% CI, cases intervention versus control) were 0.76 (0.49-1.18; 36 vs. 45) for vitamin D3, 0.70 (0.44-1.09, 32 vs. 49) for omega-3s, and 0.74 (0.48-1.15, 35 vs. 46) for SHEP. For combinations of two treatments, adjusted HRs were 0.53 (0.28-1.00; 15 vs. 28 cases) for omega-3s plus vitamin D3; 0.56 (0.30-1.04; 11 vs. 21) for vitamin D3 plus SHEP; and 0.52 (0.28-0.97; 12 vs. 26 cases) for omega-3s plus SHEP. For all three treatments combined, the adjusted HR was 0.39 (0.18-0.85; 4 vs. 12 cases). Conclusion: Supplementation with daily high-dose vitamin D3 plus omega-3s, combined with SHEP, showed cumulative reduction in the cancer risk in generally healthy and active and largely vitamin D-replete adults ≥70 years. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT01745263.

Vitamin D: Bolus Is Bogus-A Narrative Review.

In this review we summarize the impact of bolus versus daily dosing of vitamin D on 25(OH)D and 1,25(OH)2D levels, as well as on key countervailing factors that block vitamin D functions at the cellular level. Further, we discuss the role of bolus versus daily dosing of vitamin D for several health outcomes, including respiratory infections and coronavirus disease 2019 (COVID-19), rickets, falls and fractures, any cancer, and cancer-related mortality. This discussion appears timely because bolus doses continue to be tested for various disease outcomes despite a growing amount of evidence suggesting lack of efficacy or even detrimental effects of bolus dosing of vitamin D for outcomes where daily dosing at modest levels was effective in the vitamin D deficient. As a result, these discordant results may bias health recommendations for vitamin D if the recommendations are based on meta-analyses combining both daily and bolus dosing trials. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Sufficient Plasma Vitamin C Is Related to Greater Bone Mineral Density among Postmenopausal Women from the Boston Puerto Rican Health Study.

BACKGROUND: Vitamin C may benefit bone as an antioxidant. OBJECTIVES: This cross-sectional study evaluated associations between dietary, supplemental, and plasma vitamin C with bone mineral density (BMD) among Puerto Rican adults. METHODS: Diet was assessed by food-frequency questionnaire (n = 902); plasma vitamin C, measured in fasting blood (n = 809), was categorized as sufficient (≥50 µmol/L), insufficient (20-49 µmol/L), or low (<20 µmol/L). Associations between vitamin C and BMD (measured by DXA) were tested, with false discovery rate correction for multiple comparisons, and interactions by smoking, sex, and estrogen status. Least-squares mean BMDs were compared across tertiles of diet and plasma vitamin C. RESULTS: Participants' mean age was 59 ± 7 y (range: 46-78 y), 72% were women, mean dietary vitamin C was 95 ± 62 mg/d, and plasma vitamin C ranged from 1.7 to 125 µmol/L. No associations were observed between dietary vitamin C and BMD (P-value range: 0.48-0.96). BMD did not differ by vitamin C supplement use (P-value range: 0.07-0.29). Total femur BMD was higher (P = 0.04) among plasma vitamin C-sufficient participants (mean: 1.06; 95% CI: 1.035, 1.076 g/cm2) compared with low plasma vitamin C participants (1.026; 0.999, 1.052 g/cm2) in adjusted models. Findings at the trochanter were similar (P = 0.04). Postmenopausal women without estrogen therapy, with sufficient plasma vitamin C, showed greater total femur BMD (1.004 ± 0.014 g/cm2) compared to those with low plasma vitamin C (0.955 ± 0.017 g/cm2; P = 0.001). Similar findings were observed at the trochanter (P < 0.001). No significant associations were observed among premenopausal women or those with estrogen therapy or men. Interactions with smoking status were not significant. CONCLUSIONS: Dietary vitamin C was not associated with BMD. Low plasma vitamin C, compared with sufficiency, was associated with lower hip BMD, particularly among postmenopausal women without estrogen therapy. Future research is needed to determine whether vitamin C status is associated with change in BMD or reduction in fracture risk.

Assessment of the performance of the SarQoL® questionnaire in screening for sarcopenia in older people.

BACKGROUND: Because of its low prevalence and the need for physical tests to establish a diagnosis, recruiting sarcopenic people for clinical studies can be a resource-intensive process. AIMS: We investigated whether the SarQoL®, a 55-item questionnaire designed to measure quality of life in sarcopenia, could be used to identify older people with a high likelihood of being sarcopenic, and to compare its performance to the SARC-F tool. METHODS: We performed a secondary analysis of data from older, community-dwelling participants of the SarcoPhAge study, evaluated for sarcopenia according to the EWGSOP2 criteria, and who completed the SarQoL® and SARC-F questionnaires. We determined the optimal threshold to distinguish between sarcopenic and non-sarcopenic people with the Youden index. Screening performance was evaluated with the area under the curve (AUC) and by calculating sensitivity and specificity. RESULTS: The analysis of 309 participants provided an optimal threshold value of ≤ 52.4 points for identifying people with sarcopenia with the SarQoL® questionnaire, which resulted in a sensitivity of 64.7% (41.1-84.2%), a specificity of 80.5% (75.7-84.7%) and an AUC of 0.771 (0.652-0.889). Compared to the SARC-F, the SarQoL® has greater sensitivity (64.7% vs 52.39%), but slightly lower specificity (80.5% vs. 86.6%). DISCUSSION: The SarQoL® questionnaire showed acceptable screening accuracy, on par with the SARC-F. The optimal threshold of ≤ 52.4 points should be confirmed in other cohorts of older people. CONCLUSIONS: This exploratory study showed that the SarQoL® could potentially be applied in a screening strategy, with the added benefit of providing a measure of QoL at the same time.

Controversies in Vitamin D: A Statement From the Third International Conference.

The Third International Conference on Controversies in Vitamin D was held in Gubbio, Italy, September 10-13, 2019. The conference was held as a follow-up to previous meetings held in 2017 and 2018 to address topics of controversy in vitamin D research. The specific topics were selected by the steering committee of the conference and based upon areas that remain controversial from the preceding conferences. Other topics were selected anew that reflect specific topics that have surfaced since the last international conference. Consensus was achieved after formal presentations and open discussions among experts. As will be detailed in this article, consensus was achieved with regard to the following: the importance and prevalence of nutritional rickets, amounts of vitamin D that are typically generated by sun exposure, worldwide prevalence of vitamin D deficiency, the importance of circulating concentrations of 25OHD as the best index of vitamin D stores, definitions and thresholds of vitamin D deficiency, and efficacy of vitamin D analogues in the treatment of psoriasis. Areas of uncertainly and controversy include the following: daily doses of vitamin D needed to maintain a normal level of 25OHD in the general population, recommendations for supplementation in patients with metabolic bone diseases, cutaneous production of vitamin D by UVB exposure, hepatic regulation of 25OHD metabolites, definition of vitamin D excess, vitamin D deficiency in acute illness, vitamin D requirements during reproduction, potential for a broad spectrum of cellular and organ activities under the influence of the vitamin D receptor, and potential links between vitamin D and major human diseases. With specific regard to the latter area, the proceedings of the conference led to recommendations for areas in need of further investigation through appropriately designed intervention trials. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Effect of daily 2000 IU versus 800 IU vitamin D on blood pressure among adults age 60 years and older: a randomized clinical trial.

BACKGROUND: Observational studies report higher blood pressure (BP) among individuals with lower 25-hydroxyvitamin D concentration. Whether dosage of vitamin D supplementation has a differential effect on BP control remains unclear. OBJECTIVE: The study aimed to determine if daily vitamin D supplementation with 2000 IU is more effective than 800 IU for BP control among older adults. METHODS: This randomized, double-blind, ancillary trial of the Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis enrolled adults aged ≥60 y who underwent elective surgery due to severe knee osteoarthritis. Participants were randomly assigned to receive high dose (2000 IU) or standard dose (800 IU) daily vitamin D3 for 24 mo. Outcomes included daytime and 24-h mean systolic BP. BP variability and serum 25-hydroxyvitamin D concentration were examined in a post hoc and observational analysis. RESULTS: Of the 273 participants randomly assigned, 250 participants completed a follow-up 24-h ambulatory BP monitoring (mean age: 70.4 ± 6.4 y; 47.2% men). The difference in daytime mean systolic BP reduction between the 2000 IU (n = 123) and 800 IU (n = 127) groups was not statistically significant (-2.75 mm Hg vs. -3.94 mm Hg; difference: 1.18 mm Hg; 95% CI: -0.68, 3.05; P = 0.21), consistent with 24-h mean systolic BP. However, systolic BP variability was significantly reduced with 2000 IU (average real variability: -0.37 mm Hg) compared to 800 IU vitamin D3 (0.11 mm Hg; difference: -0.48 mm Hg; 95% CI: -0.94, -0.01; P = 0.045). Independent of group allocation, maximal reductions in mean BP were observed at 28.7 ng/mL of achieved serum 25-hydroxyvitamin D concentrations. CONCLUSIONS: While daily 2000 IU and 800 IU vitamin D3 reduced mean systolic BP over 2 y to a small and similar extent, 2000 IU reduced mean systolic BP variability significantly more compared with 800 IU. However, without a placebo control group we cannot ascertain whether vitamin D supplementation effectively reduces BP.This trial was registered at www.clinicaltrials.gov as NCT00599807.

Knowledge, attitudes, beliefs, and health behaviors of bone health among Caribbean Hispanic/Latino adults.

Few studies have examined knowledge and perceptions of osteoporosis among Caribbean Latino adults. Confusion regarding the term osteoporosis was noted. Doctors were viewed as trusted sources of health information, although descriptions of a paradoxical relationship emerged. This study can be used to inform culturally tailored interventions for osteoporosis prevention. PURPOSE: The overall goal of this study was to assess knowledge, attitudes, and beliefs of bone health and osteoporosis among Caribbean Latino adults aged > 50 years. METHODS: This triangulated mixed methods study included completion of a quantitative questionnaire and participation in one of four focus groups to obtain information on (1) general health, (2) knowledge about bone health and osteoporosis, (3) sources of information about bone health, and (4) prevention knowledge and personal responsibility. Quantitative data were analyzed using SAS, and qualitative data were analyzed using descriptive and structural coding by two independent research members. RESULTS: The majority of participants were female (73%), Dominican (84%), and low income (82% < $20,000) with a mean age of 68.4 (± 8.5) years. Most participants had heard of osteoporosis (90%); however, the majority were not able to accurately describe this chronic condition. Health care providers were viewed as most trusted sources of health information, despite feelings of being rushed during their visits, with limited communication about preventative care. Most participants felt that nutrition and exercise were important for overall health. CONCLUSIONS: Caribbean Hispanic adults in this study reported knowledge of osteoporosis and nutritional factors associated with prevention of this chronic condition. However, qualitatively, there was confusion between osteoporosis and other bone and joint conditions. Culturally specific interventions to promote prevention of osteoporosis are urgently needed for this underserved, high-risk population.

Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions.

The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D-deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.

Effect of 800 IU Versus 2000 IU Vitamin D3 With or Without a Simple Home Exercise Program on Functional Recovery After Hip Fracture: A Randomized Controlled Trial.

OBJECTIVES: To evaluate 2 simple strategies, vitamin D3 and a home exercise program, in functional recovery during the first year after hip fracture. DESIGN: Secondary analysis of a factorial clinical trial. Patients were randomly allocated to 800 IU (standard of care) or 2000 IU vitamin D3 and a daily instruction of a simple home exercise program (SHEP) or standard physiotherapy alone during acute care. SETTING AND PARTICIPANTS: Acute hip fracture patients aged ≥65 years, after hip fracture surgery, admitted to a large hospital in Zurich, Switzerland. MEASURES: Three objective measures of lower extremity function were assessed at baseline and 6 and 12 months, with the Timed Up and Go test (TUG) as the primary endpoint, and knee flexor and extensor strength, and a self-reported physical function score (PF-10) as secondary endpoints. Linear mixed model regression analyses were based on intention to treat, adjusting for baseline function, time, age, sex, and baseline 25-hydroxyvitamin D level. RESULTS: We enrolled 173 patients (79.2% women; mean age 84 years; 77.5% living at home). A significant interaction was found between vitamin D3 dose and SHEP for TUG (P = .045). Thus, findings compared the standard of care reference arm with 800 IU vitamin D3 without SHEP to 3 interventions arms (800 IU vitamin D3+SHEP; 2000 IU vitamin D3 without SHEP; 2000 IU vitamin D3+SHEP). For TUG, over 12 months the 800 IU vitamin D3+SHEP group performed significantly better than the standard-of-care group (13.8 vs 19.5 seconds; P = .01). Findings for knee flexor strength were in line with TUG results and approached significance (P = .07), whereas knee extensor strength and PF-10 did not differ by treatments. CONCLUSIONS/IMPLICATIONS: For functional recovery after hip fracture, combining home exercise with 800 IU vitamin D3 is superior to no home exercise or 2000 IU vitamin D3. None of the interventions improved subjective physical functioning.

Association between 25-Hydroxyvitamin D Status and Components of Body Composition and Glucose Metabolism in Older Men and Women.

Obesity and sarcopenia are major causes of morbidity and mortality among seniors. Vitamin D deficiency is very common especially among seniors and has been associated with both muscle health and obesity. This study investigated if 25-hydroxyvitamin D (25(OH)D) status is associated with body composition and insulin resistance using baseline data of a completed RCT among relatively healthy community-dwelling seniors (271 seniors age 60+ years undergoing elective surgery for unilateral total knee replacement due to osteoarthritis). Cross-sectional analysis compared appendicular lean mass index (ALMI: lean mass kg/height m²) and fat mass index (FMI: fat mass kg/height m²) assessed by DXA and insulin resistance between quartiles of serum 25(OH)D concentration using multivariable linear regression adjusted for age, sex, smoking status, physical activity, and body mass index (BMI). Participants in the lowest serum 25(OH)D quartile (4.7⁻17.5 ng/mL) had a higher fat mass (9.3 kg/m²) compared with participants in the third (8.40 kg/m²; Q3 = 26.1⁻34.8 ng/mL) and highest (8.37 kg/m²; Q4 = 34.9⁻62.5 ng/mL) quartile (poverall = 0.03). Higher serum 25(OH)D quartile status was associated with higher insulin sensitivity (poverall = 0.03) and better beta cell function (p = 0.004). Prevalence of insulin resistance tended to be higher in the second compared with the highest serum 25(OH)D quartile (14.6% vs. 4.8%, p = 0.06). Our findings suggest that lower serum 25(OH)D status may be associated with greater fat mass and impaired glucose metabolism, independent of BMI and other risk factors for diabetes.

Recovery after unilateral knee replacement due to severe osteoarthritis and progression in the contralateral knee: a randomised clinical trial comparing daily 2000 IU versus 800 IU vitamin D.

OBJECTIVE: To test whether daily high-dose vitamin D improves recovery after unilateral total knee replacement. METHODS: Data come from a 24-month randomised, double-blind clinical trial. Adults aged 60 and older undergoing unilateral joint replacement due to severe knee osteoarthritis were 6-8 weeks after surgery randomly assigned to receive daily high-dose (2000 IU) or standard-dose (800 IU) vitamin D3. The primary endpoints were symptoms (Western Ontario and McMaster Universities Arthritis Index pain and function scores) assessed at baseline, 6, 12, 18 and 24 months in both knees, and the rate of falls over 24 months. The secondary outcomes were sit-to-stand performance, gait speed, physical activity and radiographic progression in the contralateral knee. RESULTS: We recruited 273 participants, 137 were randomised to receive 2000 IU and 136 were randomised to receive 800 IU vitamin D per day. 2000 IU vitamin D increased 25-hydroxyvitamin D levels to 45.6 ng/mL and 800 IU vitamin D to 37.1 ng/mL at month 24 (p<0.0001). While symptoms improved significantly in the operated knee and remained stable in the contralateral knee over time, none of the primary or secondary endpoints differed by treatment group over time. The rate of falls over 24 months was 1.05 with 2000 IU and 1.07 with 800 IU (p=0.84). 30.5% of participants in the 2000 IU and 31.3% of participants in the 800 IU group had radiographic progression in the contralateral knee over 24 months (p=0.88). CONCLUSIONS: Our findings suggest that a 24-month treatment with daily 2000 IU vitamin D did not show greater benefits or harm than a daily standard dose of 800 IU among older adults undergoing unilateral total knee replacement.

Pitfalls in the measurement of muscle mass: a need for a reference standard.

BACKGROUND: All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass. Thus, the objective measurement of sarcopenia is hampered by limitations intrinsic to assessment tools. The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard. METHODS: Literature reviews were performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis working group on frailty and sarcopenia. Face-to-face meetings were organized for the whole group to make amendments and discuss further recommendations. RESULTS: A wide range of techniques can be used to assess muscle mass. Cost, availability, and ease of use can determine whether the techniques are better suited to clinical practice or are more useful for research. No one technique subserves all requirements but dual energy X-ray absorptiometry could be considered as a reference standard (but not a gold standard) for measuring muscle lean body mass. CONCLUSIONS: Based on the feasibility, accuracy, safety, and low cost, dual energy X-ray absorptiometry can be considered as the reference standard for measuring muscle mass.

Nutrients and bioactives in green leafy vegetables and cognitive decline: Prospective study.

OBJECTIVE: To increase understanding of the biological mechanisms underlying the association, we investigated the individual relations to cognitive decline of the primary nutrients and bioactives in green leafy vegetables, including vitamin K (phylloquinone), lutein, ß-carotene, nitrate, folate, kaempferol, and α-tocopherol. METHODS: This was a prospective study of 960 participants of the Memory and Aging Project, ages 58-99 years, who completed a food frequency questionnaire and had ≥2 cognitive assessments over a mean 4.7 years. RESULTS: In a linear mixed model adjusted for age, sex, education, participation in cognitive activities, physical activities, smoking, and seafood and alcohol consumption, consumption of green leafy vegetables was associated with slower cognitive decline; the decline rate for those in the highest quintile of intake (median 1.3 servings/d) was slower by ß = 0.05 standardized units (p = 0.0001) or the equivalent of being 11 years younger in age. Higher intakes of each of the nutrients and bioactives except ß-carotene were individually associated with slower cognitive decline. In the adjusted models, the rates for the highest vs the lowest quintiles of intake were ß = 0.02, p = 0.002 for phylloquinone; ß = 0.04, p = 0.002 for lutein; ß = 0.05, p < 0.001 for folate; ß = 0.03, p = 0.02 for α-tocopherol; ß = 0.04, p = 0.002 for nitrate; ß = 0.04, p = 0.003 for kaempferol; and ß = 0.02, p = 0.08 for ß-carotene. CONCLUSIONS: Consumption of approximately 1 serving per day of green leafy vegetables and foods rich in phylloquinone, lutein, nitrate, folate, α-tocopherol, and kaempferol may help to slow cognitive decline with aging.

Association between Caregiver Role and Short- and Long-Term Functional Recovery after Hip Fracture: A Prospective Study.

OBJECTIVES: After a hip fracture, 50% of senior patients are left with permanent functional decline and 30% lose their autonomy. The aim of this prospective study was to evaluate whether seniors who are in a caregiver role have better functional recovery after hip fracture compared with noncaregivers. DESIGN: Prospective observational study. SETTING: A total of 107 Swiss patients with acute hip fracture age 65 years and older (84% women; 83.0 ± 6.9 years; 87% community-dwelling). MEASUREMENTS: At baseline, participants were asked if they were caregivers for a person, a pet, or a plant. Lower-extremity mobility was measured using the Timed Up and Go (TUG) test at baseline during acute care (day 1-12 after hip fracture surgery) and at 6 and 12 months follow-up. Subjective physical functioning (SPF) was rated for prefracture values and at 6 and 12 months follow-up using the Short Form 36 Health Survey questionnaire. Differences in TUG performance or SPF between caregivers and noncaregivers at 6 and 12 months were assessed using multivariable repeated-measures analysis adjusted for age, sex, body mass index, Charlson comorbidity index, Mini-Mental State Examination, living condition, baseline TUG, and treatment (vitamin D, home exercise program as part of the original trial). RESULTS: At baseline, adjusted TUG performance was better in caregivers of any kind compared with noncaregivers (40.9 vs 84.4 seconds, P < .0001). At 6 months, and after adjustment for baseline TUG performance and other covariates, TUG was better in caregivers of any kind (-6.4 seconds, P = .007) and caregivers of plants (-6.6 seconds, P = .003) compared with noncaregivers. At 12 months, only caregivers of persons had better TUG performance compared with noncaregivers (-7.3 seconds, P = .009). Moreover, at 12 months, SPF was better in caregivers of persons (58.9 vs 45.6, P = .01) and caregivers of any kind (50.8 vs 39.3, P = .02) compared with noncaregivers. CONCLUSIONS: Senior hip fracture patients who have a caregiver role of any kind, and especially of plants, had better short-term recovery after hip fracture assessed with the TUG. For long-term recovery, senior hip fracture patients who are caregivers for other persons appeared to have a significant benefit. These benefits were independent of baseline function and all other covariates.

The authors reply: Letter on: "Pitfalls in the measurement of muscle mass: a need for a reference standard" by Clark et al.

However, semantics aside, we think that DXA can indeed serve as a reference standard for measuring muscle mass. Obviously, CT and MRI are advanced techniques that can and have been used to obtain important information such as muscle size/volume and more recently amount and distribution of intra- and intermuscular adipose tissue. Also individual muscles can be assessed separately. However, with respect to muscle mass, the comparison of DXA with CT/MRI is rather difficult because DXA and QCT/MRI measure different physical parameters.

Association between Sleep Duration, Insomnia Symptoms and Bone Mineral Density in Older Boston Puerto Rican Adults.

OBJECTIVE: To examine the association between sleep patterns (sleep duration and insomnia symptoms) and total and regional bone mineral density (BMD) among older Boston Puerto Rican adults. MATERIALS/METHODS: We conducted a cross-sectional study including 750 Puerto Rican adults, aged 47-79 y living in Massachusetts. BMD at 3 hip sites and the lumbar spine were measured using dual-energy X-ray absorptiometry. Sleep duration (≤5 h, 6 h, 7 h, 8 h, or ≥9 h/d) and insomnia symptoms (difficulty initiating sleep, difficulty maintaining sleep, early-morning awaking, and non-restorative sleep) were assessed by a questionnaire. Multivariable regression was used to examine sex-specific associations between sleep duration, insomnia symptoms and BMD adjusting for standard confounders and covariates. RESULTS: Men who slept ≥9h/d had significantly lower femoral neck BMD, relative to those reporting 8 h/d sleep, after adjusting for age, education level, smoking, physical activity, depressive symptomatology, comorbidity and serum vitamin D concentration. This association was attenuated and lost significance after further adjustment for urinary cortisol and serum inflammation biomarkers. In contrast, the association between sleep duration and BMD was not significant in women. Further, we did not find any significant associations between insomnia symptoms and BMD in men or women. CONCLUSIONS: Our study does not support the hypothesis that shorter sleep duration and insomnia symptoms are associated with lower BMD levels in older adults. However, our results should be interpreted with caution. Future studies with larger sample size, objective assessment of sleep pattern, and prospective design are needed before a conclusion regarding sleep and BMD can be reached.