Effects of Vitamin D with Calcium and Associations of Mean 25-Hydroxyvitamin D Levels with 3-Year Change in Muscle Performance in Healthy Older Adults in the Boston STOP IT Trial.

PURPOSE: The purpose of this analysis was to assess whether (1) daily vitamin D3 plus calcium supplementation vs. placebo or (2) the mean 25-hydroxyvitamin D [25(OH)D] level achieved during a 3-year trial was associated with muscle performance or balance in the Boston STOP IT study. Methods We conducted exploratory analyses in 386 men and women age 65 years and older who participated in the Boston STOP IT trial and had one or more muscle performance or balance assessments at baseline and 3 years. Participants were treated with 700 IU of vitamin D3 plus 500 mg of calcium or with double placebo daily for 3 years. Plasma 25(OH)D was measured at baseline, 6, 12, 18, 24, and 36 months; muscle performance (timed walk, grip strength, and chair-rise) and two balance tests, the one-leg stand and tandem stand, were assessed at baseline and 3 years only. Results Supplementation with vitamin D3 and calcium had no favorable effect on any muscle performance measure. The 3-year mean 25(OH)D levels were 22.7 ± 6.3 (SD) in the placebo and 30.8 ± 7.5 ng/ml in the supplemented groups (p < 0.001). The 3-year mean 25(OH)D level was positively associated with change in one-leg stand time (p = 0.04), but not with the other measures. Conclusion Vitamin D3 and calcium supplementation had no favorable effect on muscle performance or balance in this relatively healthy older population. A higher 3-year mean 25(OH)D level may favor balance, as indicated by longer one-leg stand time, but this observation should be confirmed.

Consensus statement from 2nd International Conference on Controversies in Vitamin D.

The 2nd International Conference on Controversies in Vitamin D was held in Monteriggioni (Siena), Italy, September 11-14, 2018. The aim of this meeting was to address ongoing controversies and timely topics in vitamin D research, to review available data related to these topics and controversies, to promote discussion to help resolve lingering issues and ultimately to suggest a research agenda to clarify areas of uncertainty. Several issues from the first conference, held in 2017, were revisited, such as assays used to determine serum 25-hydroxyvitamin D [25(OH)D] concentration, which remains a critical and controversial issue for defining vitamin D status. Definitions of vitamin D nutritional status (i.e. sufficiency, insufficiency and deficiency) were also revisited. New areas were reviewed, including vitamin D threshold values and how they should be defined in the context of specific diseases, sources of vitamin D and risk factors associated with vitamin D deficiency. Non-skeletal aspects related to vitamin D were also discussed, including the reproductive system, neurology, chronic kidney disease and falls. The therapeutic role of vitamin D and findings from recent clinical trials were also addressed. The topics were considered by 3 focus groups and divided into three main areas: 1) "Laboratory": assays and threshold values to define vitamin D status; 2) "Clinical": sources of vitamin D and risk factors and role of vitamin D in non-skeletal disease and 3) "Therapeutics": controversial issues on observational studies and recent randomized controlled trials. In this report, we present a summary of our findings.

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.

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.

Correction to: Global dietary calcium intake among adults: a systematic review.

The original Electronic Supplementary Material file 3 contained an erroneous reference for Mali. A link to the corrected file is provided here.

Does nutrition play a role in the prevention and management of sarcopenia?

There is a growing body of evidence that links nutrition to muscle mass, strength and function in older adults, suggesting that it has an important role to play both in the prevention and management of sarcopenia. This review summarises the discussions of a working group [ESCEO working group meeting 8th September 2016] that met to review current evidence and to consider its implications for preventive and treatment strategies. The review points to the importance of 'healthier' dietary patterns that are adequate in quality in older age, to ensure sufficient intakes of protein, vitamin D, antioxidant nutrients and long-chain polyunsaturated fatty acids. In particular, there is substantial evidence to support the roles of dietary protein and physical activity as key anabolic stimuli for muscle protein synthesis. However, much of the evidence is observational and from high-income countries. Further high-quality trials, particularly from more diverse populations, are needed to enable an understanding of dose and duration effects of individual nutrients on function, to elucidate mechanistic links, and to define optimal profiles and patterns of nutrient intake for older adults.

The impact of the new National Bone Health Alliance (NBHA) diagnostic criteria on the prevalence of osteoporosis in the United States: supplementary presentation.

We evaluated the prevalence of osteoporosis using the osteoporosis diagnostic criteria developed by the National Bone Health Alliance (NBHA), which includes qualified fractures, FRAX score in addition to BMD. The expanded definition increases the prevalence compared to BMD alone definitions; however, it may better identify those at elevated fracture risk. Recently an NBHA working Group published a paper in OI with recommendations for expanding the criteria that would constitute an osteoporosis diagnosis in postmenopausal women and in men over age 50 for use in the US - Siris et al., Osteoporosis International 25(%): 1439-1443, 2014. The recommendations have now been endorsed by NOF, ASBMR and a number of professional medical groups and appear in the NOF Clinician's Guide. The new diagnostic criteria continue to include a T-score by DXA of spine or hip that is less than or equal to -2.5, but alternatively also include a hip fracture with or without BMD testing or a vertebral, pelvis, proximal humerus and in some cases a distal forearm fracture in a person with low bone mass, or a FRAX score that meets or exceeds the NOF Guide osteoporosis treatment cut point.

Increasing alkali supplementation decreases urinary nitrogen excretion when adjusted for same day nitrogen intake.

We examined whether escalating doses of potassium bicarbonate (KHCO3) supplements alter urinary nitrogen excretion expressed as a ratio to same day nitrogen intake (measure of muscle-protein breakdown). The ratio declined significantly from placebo to low to high dose of KHCO3 supplementation in older adults over 3 months, suggesting muscle-sparing. INTRODUCTION: Neutralization of dietary acid load with alkali supplementation (i.e., KHCO3) has been hypothesized to have muscle protein-sparing effects. In controlled feeding studies with fixed nitrogen (N) intake/day, 24-h urinary N excretion is a good marker of muscle breakdown. However, in studies with self-selected diets, changes in 24-h urinary N excretion can be influenced by shifts in N intake. METHODS: We evaluated changes in 24-h total urinary N excretion as a ratio of N excretion to concurrent N intake in 233 older men and women who participated in an 84-day KHCO3 supplementation randomized placebo-controlled trial. RESULTS: After adjustment for relevant cofactors, escalating doses of KHCO3 (1 mmol/kg/day [low] or 1.5 mmol/kg/day [high]) resulted in a progressive decline in urinary N excretion/N intake compared to placebo (overall P for trend = 0.042). The 84-day change in urinary N excretion/N intake in the high-dose KHCO3 group was statistically significantly lower compared to placebo (P = 0.012) but not compared to the low-dose KHCO3 group (P = 0.276). The 84-day change in urinary N excretion/N intake in the low-dose KHCO3 group did not differ significantly from placebo (P = 0.145). CONCLUSIONS: Urinary N excretion expressed as ratio to same day N intake declined steadily with increasing doses of KHCO3 supplementation from low 1 mmol/kg/day to high 1.5 mmol/kg/day, suggesting a nitrogen-sparing effect. Compared to urinary N excretion alone, this ratio could be a more reasonable measure of muscle protein metabolism in large-scale long-term human studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT1475214.

The role of calcium supplementation in healthy musculoskeletal ageing : An expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF).

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis.

Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation.

UNLABELLED: The aim was to meta-analyze randomized controlled trials of calcium plus vitamin D supplementation and fracture prevention. Meta-analysis showed a significant 15 % reduced risk of total fractures (summary relative risk estimate [SRRE], 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). INTRODUCTION: Calcium plus vitamin D supplementation has been widely recommended to prevent osteoporosis and subsequent fractures; however, considerable controversy exists regarding the association of such supplementation and fracture risk. The aim was to conduct a meta-analysis of randomized controlled trials [RCTs] of calcium plus vitamin D supplementation and fracture prevention in adults. METHODS: A PubMed literature search was conducted for the period from July 1, 2011 through July 31, 2015. RCTs reporting the effect of calcium plus vitamin D supplementation on fracture incidence were selected from English-language studies. Qualitative and quantitative information was extracted; random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) for total and hip fractures. Statistical heterogeneity was assessed using Cochran's Q test and the I (2) statistic, and potential for publication bias was assessed. RESULTS: Of the citations retrieved, eight studies including 30,970 participants met criteria for inclusion in the primary analysis, reporting 195 hip fractures and 2231 total fractures. Meta-analysis of all studies showed that calcium plus vitamin D supplementation produced a statistically significant 15 % reduced risk of total fractures (SRRE, 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). Numerous sensitivity and subgroup analyses produced similar summary associations. A limitation is that this study utilized data from subgroup analysis of the Women's Health Initiative. CONCLUSIONS: This meta-analysis of RCTs supports the use of calcium plus vitamin D supplements as an intervention for fracture risk reduction in both community-dwelling and institutionalized middle-aged to older adults.

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.

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.

Mild to moderate cognitive impairment is a major risk factor for mortality and nursing home admission in the first year after hip fracture.

BACKGROUND: It is not well established if and to what extent mild to moderate cognitive impairment predicts mortality and risk of nursing home admission after hip fracture. OBJECTIVE: To investigate prospectively whether and to what extent mild to moderate cognitive impairment, contributes to mortality and admission to nursing home in the first year after acute hip fracture. METHODS: We enrolled 173 patients with acute hip fracture age 65 and older who reached a Mini-Mental State Examination (MMSE) score of at least 15 during acute care after hip fracture repair. An MMSE score of 15 to 24 (median) was classified as mild to moderate cognitive impairment. Primary outcomes were mortality in all and admission to nursing home among seniors who lived at home prior to their hip fracture. Follow-up was 12 months with clinical visits at baseline, 6, and 12 months, plus monthly phone calls. We used Cox proportional hazards models controlling for age, sex, body mass index, baseline number of comorbidities and 25-hydroxyvitamin D status, and severe incident infections to assess the risk of mortality and nursing home admission. Because the study population was enrolled in a factorial design clinical trial testing high dose vitamin D and/or an exercise home program, all analyses also controlled for these treatment strategies. RESULTS: Of 173 acute hip fracture patients enrolled, 79% were women, 77% were admitted from home, and 80% were vitamin D deficient (<20ng/ml). Mean age was 84 years. 54% had mild to moderate cognitive impairment. Over the 12-month follow-up, 20 patients died (27% of 173) and 47 (35% of 134) were newly admitted to a nursing home. Mild to moderate cognitive impairment was associated with a more than 5-fold increased risk of mortality (HR=5.77; 95% CI: 1.55-21.55) and a more than 7-fold increased risk of nursing home admission (HR=7.37; 95% CI: 1.75-30.95). Additional independent risk factors of mortality were male gender (HR=3.55; 95% CI: 1.26-9.97), low BMI (HR=7.25; 95% CI: 1.61-33.74), and baseline 25-hydroxyvitamin D level (per 1ng/ml: HR=0.93; 95% CI: 0.87-0.998; p=0.04). CONCLUSIONS: Mild to moderate cognitive impairment in patients with acute hip fracture is associated with a high risk of mortality and nursing home admission during the first year after hip fracture. Female gender, a greater BMI and a higher 25-hydroxyvitamin D status may protect against mortality after hip fracture independent of cognitive function.

Benefit-risk assessment of vitamin D supplementation.

UNLABELLED: Current intake recommendations of 200 to 600 IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D. INTRODUCTION: This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk. METHODS AND RESULTS: Based on double-blind randomized control trials (RCTs), eight for falls (n = 2426) and 12 for non-vertebral fractures (n = 42,279), there was a significant dose-response relationship between higher-dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for 700 to 1000 IU vitamin D per day or mean 25(OH)D between 75 and 110 nmol/l (30-44 ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median between 75 and 110 nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000 IU per day or achieved 25(OH)D up to 643 nmol/l. Mean levels of 75 to 110 nmol/l were reached in most RCTs with 1,800 to 4,000 IU vitamin D per day without risk. CONCLUSION: Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the population.

Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials.

OBJECTIVE: To test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals. DATA SOURCES: We searched Medline, the Cochrane central register of controlled trials, BIOSIS, and Embase up to August 2008 for relevant articles. Further studies were identified by consulting clinical experts, bibliographies, and abstracts. We contacted authors for additional data when necessary. Review methods Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1alpha-hydroxyvitamin D(3) (1alpha-hydroxycalciferol) or 1,25-dihydroxyvitamin D(3) (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion. RESULTS: Eight randomised controlled trials (n=2426) of supplemental vitamin D met our inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D(3) concentration (25(OH)D concentration: <60 nmol/l v >or=60 nmol/l; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71 to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/l or more resulted in a 23% fall reduction (pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to 1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to 1.84). Two randomised controlled trials (n=624) of active forms of vitamin D met our inclusion criteria. Active forms of vitamin D reduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94). CONCLUSIONS: Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.

Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants.

UNLABELLED: In 17 adults on a fixed metabolic diet, an 11-day course of cinacalcet increased serum gastrin and basal gastric acid output, but not maximal gastric acid output, compared with a placebo. These findings indicate that the calcium sensor receptor plays a role in the regulation of gastric acid. INTRODUCTION: Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cinacalcet, a CaR allosteric agonist, increases serum gastrin and gastric acid secretion. METHODS: Seventeen healthy adults with normal gastric acid output were placed on an 18-day metabolic diet. On day 8 (baseline), participants were given cinacalcet (15 then 30 mg/day) or placebo for 11 days. Changes in gastric acid output, serum gastrin, and other measures were compared in the two groups. RESULTS: Changes in serum gastrin and basal acid output (adjusted for baseline body weight) were significantly more positive in the cinacalcet group compared with placebo (P = 0.004 and P = 0.039 respectively). Change in maximal acid output was similar in the two groups (P = 0.995). As expected, cinacalcet produced significant decreases in serum PTH (P < 0.001) and ionized calcium levels (P = 0.032), and increases in serum phosphorus levels (P = 0.001) and urinary calcium (P = 0.023). CONCLUSIONS: This study provides in vivo evidence that activation of the CaR increases serum gastrin levels and basal gastric acid secretion in healthy adults.

Additive benefit of higher testosterone levels and vitamin D plus calcium supplementation in regard to fall risk reduction among older men and women.

UNLABELLED: Higher physiologic testosterone levels among community dwelling older men and women may protect against falls, and this benefit may be further increased among those taking additional vitamin D plus calcium. INTRODUCTION: The aim of this study is to investigate sex hormone levels and fall risk in older men and women. METHODS: One hundred and ninety-nine men and 246 women age 65+ living at home were followed for 3 years after baseline assessment of sex hormones. Analyses controlled for several covariates, including baseline 25-hydroxyvitamin D, sex hormone binding globulin, and vitamin D plus calcium treatment (vitD+cal). RESULTS: Compared to the lowest quartile, men and women in the highest quartile of total testosterone had a decreased odds of falling (men: OR = 0.22; 95% CI [0.07,0.72]/ women: OR = 0.34; 95% CI [0.14,0.83]); if those individuals also took vitD+cal, the fall reduction was enhanced (men: OR = 0.16; 95% CI [0.03,0.90] / women: OR = 0.15; 95% CI [0.04,0.57]). Similarly, women in the top quartile of dihydroepiandrosterone sulfate (DHEA-S) had a lower risk of falling (OR = 0.39; 95% CI [0.16,0.93]). Other sex hormones and SHBG did not predict falling in men or women. CONCLUSIONS: Higher testosterone levels in both genders and higher DHEA-S levels in women predicted a more than 60% lower risk of falling. With vitD+cal, the anti-fall benefit of higher physiologic testosterone levels is enhanced from 78% to 84% among men and from 66% to 85% among women.

Severe vitamin D deficiency in Swiss hip fracture patients.

BACKGROUND: Most clinical guidelines for the prevention of hip fractures recommend 800 IU vitamin D per day. This dose shifted serum 25-hydroxyvitamin D levels (25(OH)D) in previous studies to between 60 and 100 nmol/l. AIM: To measure 25(OH)D levels and prevalence of vitamin D supplementation in individuals age 65+ with acute hip fracture. METHODS: 222 consecutive hip fracture patients were investigated over a 12 month period. Mean age of patients was 86 years and 77% were women. RESULTS: Mean serum 25(OH)D levels were low among hip fracture patients admitted from home (34.6 nmol/l), from assisted living (27.7 nmol/l), and from nursing homes (24 nmol/l). Severe vitamin D deficiency below 30 nmol/l was present in 60%, 80% were below 50 nmol/l, and less than 4% reached desirable levels of at least 75 nmol/l. Consistently, only 10% of hip fracture patients had any vitamin D supplementation on admission to acute care with significantly higher 25(OH)D levels among individuals supplemented with 800-880 IU/day (63.5 nmol/l). Controlling for age and gender, vitamin D supplementation, type of dwelling, and season were independently and significantly associated with 25(OH)D levels. CONCLUSION: These data provide evidence that current guidelines for the prevention of hip fractures need further effort to be translated into clinical practice.