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In the presence of an aging population, public health priorities need to evolve. As the populations gets older, the already existing pathologies have become commonplace with specific geriatric clinical syndromes like frailty, mobility disability, or cognitive impairment, among others. Sarcopenia is a good example for which geriatricians, neurologists, physiologists, nutritionists and epidemiologists need to find a consensual definition and diagnostic tool as well as guidelines for the management of clinical trials and possible treatments. The Carla Sarcopenia Task Force, which met in the south of France (Toulouse) for an expert consensus meeting called "Les Entretiens du Carla", have addressed a series of existing issues to place Sarcopenia into a nosological context: a definition which should be a composite of a change in muscle mass and a change in strength/function depending on either a progressive and chronic wasting process or an acute onset of loss of muscle mass; a recommendation for DXA and the Short Physical Performance Battery as a clinical pragmatic approach of Sarcopenia; a differentiated approach for clinical studies according to prevention or treatment objectives and depending on the sub-groups and target populations; and finally, a summary of therapeutic strategies currently recommended. The aim of "Les Entretiens du Carla", based on an expert meeting panel, was to address a series of unsolved issues in the field of Sarcopenia by combining the expert opinion with a revision of the existing literature on the topic. Through this report, the reader will appreciate the determination to find conclusions on the various issues and further studies to be developed to determine the best multidisciplinary approach needed. The Journal of Nutrition, Health & Aging©.

BACKGROUND: Since children have frequent contact with the health care system, while their young parents very often do not, screening children routinely might represent an important opportunity to target the young parents. We examined whether cardiovascular risk factors in children predicted the risk of their parents. METHODS: Five silent (hypertension, high triglycerides, high LDL-, high non-HDL-, and low HDL-cholesterol) and two clinical apparent (general and central adiposity) risk factors were compared in 2720 child-parent pairs from a well-defined sample of German elementary school children and parents. RESULTS: All clinical apparent and silent risk factors were significantly correlated between children and their parents, and most pronounced were those for three silent risk factors: HDL cholesterol, LDL cholesterol, and non-HDL cholesterol (correlation coefficient r=0.26-0.28). In multivariate models, adjusting for age and gender, child general and abdominal adiposity conferred a significant 2.9-fold and a 2.6-fold enhanced odds among parents of carrying the same risk factors. Similarly, abnormal LDL, HDL, or non-HDL among children conferred a significant 3.0-fold, 2.0-fold, or 2.9-fold increased odds among parents. The odds of parents appeared stronger if the child had the same sex only for clinical apparent risk factors, and most pronounced for general adiposity. CONCLUSIONS: Cardiovascular risk screening in children may serve as a case finding strategy for early prevention in high risk families. The inclusion of silent risk factors in a screening program of school children may be warranted for the high prevalence among children and enhanced case-finding potential among parents.

BACKGROUND: The effect of supplementation with calcium alone on risk fractures in a healthy population is not clear. OBJECTIVE: The objective was to determine whether 4 y of calcium supplementation would reduce the fracture risk during treatment and subsequent follow-up in a randomized placebo-controlled trial. DESIGN: The participants were aged

Recent evidence suggests that vitamin D deficiency has harmful effects on health and that recent vitamin D intake recommendations may be associated with better health outcomes. In this chapter, evidence is summarized from different studies that evaluate threshold levels for serum 25(OH)D levels in relation to bone mineral density (BMD), lower extremity function, dental health, risk of falls, fractures, cancer prevention, incident hypertension and mortality. For all endpoints, levels in the deficient range (50 nmol/l;20 ng/ml) are associated with no benefit or adverse effects, while the most advantageous serum levels for 25(OH)D appeared to be close to 75 nmol/l (30 ng/ml). An intake of 800 IU (20 microg) of vitamin D3 (cholecalciferol) per day for all adults may bring 97% of the population to level of at least 50 nmol/l and about 50% up to 75 nmol/l. Thus, higher doses of vitamin D than currently recommended are needed to bring most individuals to75 nmol/l. While estimates suggest that 1600 to 2000 IU vitamin D3 per day may successfully and safely achieve this goal, the implications of higher doses for the total adult population need to be addressed in future studies.

Inadequate intakes of vitamin D and calcium lead to reduced calcium absorption, higher bone remodeling rates, and increased bone loss. Vitamin D insufficiency has also been linked to reduced muscle function and increased risk of falling. The mechanisms for the performance and muscle effects are not well understood. Administering vitamin D to those with inadequate vitamin D status has been shown to lower fracture rates in some trials but not in others. The purpose of this presentation is (1) to examine how calcium and vitamin D work in concert, (2) to consider key evidence that increasing vitamin D intake will affect risk of falls and fractures, and (3) to estimate the 25-hydroxyvitamin D [25(OH)D] level needed to achieve maximum fracture protection.

To systematically review fatigue instruments used in patients with systemic lupus erythematosus (SLE) and to seek consensus on which instruments should be recommended for future studies and which data on comorbid conditions should be reported when evaluating fatigue in patients with SLE.We used data from Medline and EMBase databases (from January 1970 to June 2006), clinical experts, and bibliographies. Data were extracted independently by 4 authors and reviewed by a working group and larger expert panel to produce a recommendation. Instruments were examined for construct validity, reliability, and responsiveness to change. Correlations between fatigue and some components of the Medical Outcomes Study Short Form 36 (SF-36), disease activity, and comorbidities were reviewed.We identified 34 studies that used 15 fatigue instruments in patients with SLE. The Fatigue Severity Scale (FSS) was used in 56% of the studies. The Systemic Lupus Activity Measure was significantly correlated with fatigue, but the Systemic Lupus Erythematosus Disease Activity Index was not. Fatigue was also correlated with pain, poor quality of sleep, depression, and with each subscale of the SF-36.The working group and expert panel recommend the 9-item FSS for evaluating fatigue in SLE patients. Responsiveness to change of fatigue instruments has not been well established in SLE and needs further study. The panel suggested that an important improvement or response could be a 15% decrease in the FSS. The effect of several important confounding factors of fatigue such as sleep disorders, depression, fibromyalgia, and anemia needs to be collected and reported.

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. The aim of this study is to investigate sex hormone levels and fall risk in older men and women. 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). 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. 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.

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.

Hydroxylation of 25(OH)D to 1,25-dihydroxyvitamin D and signaling through the vitamin D receptor occur in various tissues not traditionally involved in calcium homeostasis. Laboratory studies indicate that 1,25-dihydroxyvitamin D suppresses renin expression and vascular smooth muscle cell proliferation; clinical studies demonstrate an inverse association between ultraviolet radiation, a surrogate marker for vitamin D synthesis, and blood pressure. We prospectively studied the independent association between measured plasma 25-hydroxyvitamin D [25(OH)D] levels and risk of incident hypertension and also the association between predicted plasma 25(OH)D levels and risk of incident hypertension. Two prospective cohort studies including 613 men from the Health Professionals’ Follow-Up Study and 1198 women from the Nurses’ Health Study with measured 25(OH)D levels were followed for 4 to 8 years. In addition, 2 prospective cohort studies including 38 388 men and 77 531 women with predicted 25(OH)D levels were followed for 16 to 18 years. During 4 years of follow-up, the multivariable relative risk of incident hypertension among men whose measured plasma 25(OH)D levels were

A meta-analysis of primary prevention high-quality trials published in 2005 found that oral cholecalciferol (D3) in a daily dose of 700-800 IU or intermittently 100,000 IU every 4 months with or without calcium, should reduce both hip and non-vertebral fracture risk significantly compared to placebo. Trials that administered 400 IU vitamin D did not achieve fracture efficacy. Notably, there was a significant association between higher achieved 25-hydroxyvitamin D levels (25(OH)D) in the treatment groups and fracture efficacy: The minimal mean level where fracture efficacy was observed was 74 nmol/l (25(OH)D). Epidemiological data for bone density and lower extremity strength support this threshold, and high-quality trials that used 700 to 800 IU D3 suggested fall risk reduction by 35 to 65% in institutionalized and community-dwelling older individuals. However, since the 2005 meta-analysis, benefits of vitamin D on fracture and fall reduction have been questioned by results from several recent trials. This review proposes that the interpretation of these recent trials is hindered by different doses of vitamin D, different types of supplemental vitamin D (D3 or ergocalciferol D2), low adherence, concurrent use of supplements outside the study protocol, open study design, short follow-up, and/or different patient risk profiles including primary and secondary fracture prevention. In most recent trials, low adherence, the use of the relatively less potent D2, or a too low dose of D3 (400 IU) may have prohibited a shift of (25(OH)D) levels in the treatment groups to the desirable range of at least 75 nmol/l. In summary, from recent trials, two lesson may be learned: (1) Adherence less than 60% is insufficient to achieve fracture efficacy with daily 800 IU D3 plus calcium, (2) D2 in any application or any previously studied dose may not reduce fractures in institutionalized or community-dwelling older individuals.

To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents.Secondary data analysis of a previously conducted randomized clinical trial.Seven hundred twenty-five-bed long-term care facility.One hundred twenty-four nursing home residents (average age 89).Participants were randomly assigned to receive one of four vitamin D supplement doses (200 IU, 400 IU, 600 IU, or 800 IU) or placebo daily for 5 months.Number of fallers and number of falls assessed using facility incident tracking database.Over the 5-month study period, the proportion of participants with falls was 44% in the placebo group (11/25), 58% (15/26) in the 200 IU group, 60% (15/25) in the 400 IU group, 60% (15/25) in the 600 IU group, and 20% (5/23) in the 800 IU group. Participants in the 800 IU group had a 72% lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months (rate ratio=0.28; 95% confidence interval=0.11-0.75). No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups.Nursing home residents in the highest vitamin D group (800 IU) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses. Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group.

In this large population-based study, fracture rates for hips, distal forearms, proximal humeri, and ankles were higher in winter than in other seasons, although the winter peak was small for hip fractures (p0.05 at all sites). Younger age between 65 and 80, living in warmer states and male gender were associated with increased winter morbidity due to fractures.The objective was to investigate seasonal variation in the incidence of four common fractures, and explore the association of weather with risk.Population-based analysis of individuals age 65 and older, including fractures of the hip, the distal forearm, the proximal humerus and the ankle. Weather information was obtained from the US National Oceanic and Atmospheric Administration website.For all fractures, rates were highest in winter and lowest in summer (p0.05 at all sites). Winter peaks were more pronounced in warm climate states, in men, and in those younger than 80 years old. In winter, total snowfall was associated with a reduced risk of hip fracture (-5% per 20 inches) but an increased risk of non-hip fractures (6-12%; p0.05 at all sites). In summer, hip fracture risk tended to be lower during sunny weather (- 3% per 2 weeks of sunny days; p = 0.13), while other fractures were increased (15%-20%; p0.05) in sunny weather.Fractures contribute considerably to winter morbidity in older individuals. Younger age between 65 and 80, living in warmer states and male gender are risk factors for increased winter morbidity due to fractures. Weather affects hip fracture risk differently than the other fractures studied.

Recent evidence suggests that vitamin D intakes above current recommendations may be associated with better health outcomes. However, optimal serum concentrations of 25-hydroxyvitamin D [25(OH)D] have not been defined. This review summarizes evidence from studies that evaluated thresholds for serum 25(OH)D concentrations in relation to bone mineral density (BMD), lower-extremity function, dental health, and risk of falls, fractures, and colorectal cancer. For all endpoints, the most advantageous serum concentrations of 25(OH)D begin at 75 nmol/L (30 ng/mL), and the best are between 90 and 100 nmol/L (36-40 ng/mL). In most persons, these concentrations could not be reached with the currently recommended intakes of 200 and 600 IU vitamin D/d for younger and older adults, respectively. A comparison of vitamin D intakes with achieved serum concentrations of 25(OH)D for the purpose of estimating optimal intakes led us to suggest that, for bone health in younger adults and all studied outcomes in older adults, an increase in the currently recommended intake of vitamin D is warranted. An intake for all adults of > or =1000 IU (25 microg) [DOSAGE ERROR CORRECTED] vitamin D (cholecalciferol)/d is needed to bring vitamin D concentrations in no less than 50% of the population up to 75 nmol/L. The implications of higher doses for the entire adult population should be addressed in future studies.

The dose of vitamin D in the management of osteoporosis should be no less than 700–800 IU per day. An optimal dose of vitamin D should raise serum concentrations of 25(OH)D to the desirable range of at least 75 nmol/l. Higher intermittent oral doses of vitamin D may overcome low adherence. Vitamin D supplementation in the management of osteoporosis holds a significant public health potential because of its low cost, excellent tolerability, and combined musculo-skeletal benefits. Fall and fracture prevention with vitamin D is especially appealing in the treatment of older individuals at risk for fall-related fractures. However, bone density, strength, and function benefits with vitamin D include active and inactive subgroups of community-dwelling older men and women. Based on a recent expert panel and supportive evidence presented in this review, serum concentrations of at least 75 nmol/l 25(OH)D will be referred to as desirable. Today, desirable serum 25(OH)D levels of at least 75 nmol/l may only be reached in about one third of US older individuals and even fewer European older individuals. Two main factors discussed in this review may help public health efforts to ensure desirable vitamin D levels for fall and fracture prevention, including (1) a sufficient dose of vitamin D and (2) improved adherence to supplementation.

Background: A recent meta-analysis found that cholecalciferol (vitamin D) should reduce falls by more than 20%. However, little is known about whether supplemental cholecalciferol plus calcium citrate malate will lower the long-term risk of falling in men, active older individuals, and older individuals with higher 25hydroxyvitamin D levels. Methods: We studied the effect of 3-year supplementation with cholecalciferol-calcium on the risk of falling atleastoncein199menand246women65yearsorolder and living at home. Individuals received 700 IU of cholecalciferolplus500mgofcalciumcitratemalateperday or placebo in a randomized double-blind manner. Subjects were classified as less physically active if physical activity was below the median level. Low 25hydroxyvitamin D levels were classified as those below 32 ng/mL (80 nmol/L). Results: In 3 years, 55% of women and 45% of men reported at least 1 fall. Mean±SD baseline 25hydroxyvitamin D levels were 26.6±12.7 ng/mL (66.4±31.7 nmol/L) in women and 33.2±14.2 ng/mL (82.9±34.9) in men. Cholecalciferol-calcium significantly reduced the odds of falling in women (odds ratio [OR],0.54;95%confidenceinterval[CI],0.30-0.97),but not in men (OR, 0.93; 95% CI, 0.50-1.72). Fall reductionwasmostpronouncedinlessactivewomen(OR,0.35; 95% CI, 0.15-0.81). Baseline 25-hydroxyvitamin D level did not modulate the treatment effect. Conclusions: Long-term dietary cholecalciferolcalcium supplementation reduces the odds of falling in ambulatory older women by 46%, and especially in less active women by 65%. Supplementation had a neutral effect in men independent of their physical activity level. Arch Intern Med. 2006;166:424-430

Objective To describe the association between serum 25-hydroxyvitamin D (25[OH]D) level and bone mineral density (BMD) in persons with primary knee osteoarthritis (OA). Methods We conducted a population-based survey of the Framingham Study. A total of 228 subjects with primary radiographic knee OA were identified. For vitamin D status, 25(OH)D levels ≤15 ng/ml were classified as vitamin D deficient, 25(OH)D levels 16–32 ng/ml were classified as hypovitaminosis D, and 25(OH)D levels >32 ng/ml were classified as vitamin D replete. We compared average BMD between categories of 25(OH)D levels in subjects with OA using a linear regression model while adjusting for sex, age, body mass index (BMI), knee pain, physical activity, cohort, and disease severity. Results Mean age was 74.4 years and 36% were men. Of 228 individuals, 15% were vitamin D deficient, 51% had hypovitaminosis D, and 34% were vitamin D replete. Compared with subjects with vitamin D deficiency, those with hypovitaminosis D had a 7.3% higher BMD (adjusted percent difference; P = 0.02) and vitamin D replete subjects had an 8.5% higher BMD (adjusted percent difference; P = 0.02; test for trend across categories: P = 0.04). Conclusion We observed a significant positive association between serum 25(OH)D and BMD in individuals with primary knee OA, independent of sex, age, BMI, knee pain, physical activity, and disease severity. Given the high prevalence of low 25(OH)D status in persons with knee OA and the positive association between 25(OH)D and BMD, vitamin D supplementation may enhance BMD in individuals with OA.

Emerging evidence suggests an inverse relation between vitamin D and blood pressure. We examined the independent association between intake of vitamin D and the risk of incident hypertension among participants of 3 large and independent prospective cohorts: Nurses Health Study I (NHS I; n=77 436), NHS II (n=93 803), and Health Professionals’ Follow-up Study (HPFS; n=38 074). Relative risks and 95% confidence intervals for incident hypertension were computed according to quintiles of vitamin D intake using Cox proportional hazards regression and adjusted for relevant covariates. Each cohort was followed for ≥8 years. Vitamin D intake was not associated with the risk of developing hypertension. The multivariable relative risk estimates for the highest compared with lowest quintile of intake were 0.98 (0.93 to 1.04) in NHS I, 1.13 (0.99 to 1.29) in NHS II, and 1.03 (0.93 to 1.15) in HPFS. When we compared participants who consumed ≥1600 to

The objectives were:(1) to validate a quantitative balance assessment method for fall risk prediction; (2) to investigate whether the effect of vitamin D and calcium on the risk of falling is mediated through postural or dynamic balance, as assessed by this method.A secondary analysis of a double blind randomized controlled trial was employed, which included 64 institutionalized elderly women with complete balance assessment (age range: 65-97; mean 25-hydroxyvitamin D levels: 16.4 ng/ml (SD +/-9.9). Participants received 1,200 mg calcium plus 800 IU cholecalciferol (n=33) or 1,200 mg calcium (n=31) per day over a 3-month treatment period. Using an electronic device attached to the lower back of the participant, balance was assessed as the degree of trunk angular displacement and angular velocity during a postural task (standing on two legs, eyes open, for 20 s) and a dynamic task (get up from a standard height chair with arm rests, sit down and then stand up again and remain standing).It was found that both postural and dynamic balance independently and significantly predicted the rate of falling within the 3-month follow-up. Vitamin D plus calcium reduced the rate of falls by 60% [relative risk (RR)=0.40; 95% CI: 0.17, 0.94] if compared with calcium alone. Once postural and dynamic balance were added to the regression analysis, they both attenuated the effect of vitamin D plus calcium on the rate of falls. For postural balance, the RR changed by 22% from 0.40 to 0.62 if angular displacement was added to the model, and by 9% from 0.40 to 0.49 if angular velocity was added. For dynamic balance, it changed by 1% from 0.40 to 0.41 if angular displacement was added, and by 14% from 0.40 to 0.54 if angular velocity was added.Thus, balance assessment using trunk angular displacement is a valid method for the prediction of falls in older women. Of the observed 60% reduction in the rate of falls by vitamin D plus calcium supplementation compared with calcium alone, up to 22% of the treatment effect was explained by a change in postural balance and up to 14% by dynamic balance.

ContextThe role and dose of oral vitamin D supplementation in nonvertebral fracture prevention have not been well established.ObjectiveTo estimate the effectiveness of vitamin D supplementation in preventing hip and nonvertebral fractures in older persons.Data SourcesA systematic review of English and non-English articles using MEDLINE and the Cochrane Controlled Trials Register (1960-2005), and EMBASE (1991-2005). Additional studies were identified by contacting clinical experts and searching bibliographies and abstracts presented at the American Society for Bone and Mineral Research (1995-2004). Search terms included randomized controlled trial (RCT), controlled clinical trial, random allocation,double-blind method, cholecalciferol,ergocalciferol,25-hydroxyvitamin D, fractures, humans, elderly, falls, and bone density.Study SelectionOnly double-blind RCTs of oral vitamin D supplementation (cholecalciferol, ergocalciferol) with or without calcium supplementation vs calcium supplementation or placebo in older persons (≥60 years) that examined hip or nonvertebral fractures were included.Data ExtractionIndependent extraction of articles by 2 authors using predefined data fields, including study quality indicators.Data SynthesisAll pooled analyses were based on random-effects models. Five RCTs for hip fracture (n = 9294) and 7 RCTs for nonvertebral fracture risk (n = 9820) met our inclusion criteria. All trials used cholecalciferol. Heterogeneity among studies for both hip and nonvertebral fracture prevention was observed, which disappeared after pooling RCTs with low-dose (400 IU/d) and higher-dose vitamin D (700-800 IU/d), separately. A vitamin D dose of 700 to 800 IU/d reduced the relative risk (RR) of hip fracture by 26% (3 RCTs with 5572 persons; pooled RR, 0.74; 95% confidence interval [CI], 0.61-0.88) and any nonvertebral fracture by 23% (5 RCTs with 6098 persons; pooled RR, 0.77; 95% CI, 0.68-0.87) vs calcium or placebo. No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons; pooled RR for hip fracture, 1.15; 95% CI, 0.88-1.50; and pooled RR for any nonvertebral fracture, 1.03; 95% CI, 0.86-1.24).ConclusionsOral vitamin D supplementation between 700 to 800 IU/d appears to reduce the risk of hip and any nonvertebral fractures in ambulatory or institutionalized elderly persons. An oral vitamin D dose of 400 IU/d is not sufficient for fracture prevention.

Improved standards for the evaluation of therapeutic interventions in systemic lupus erythematosus (SLE) are needed. The purpose of this study by a committee of the American College of Rheumatology was to define clinically meaningful improvement, no change, or worsening in 6 existing clinical measures of SLE disease activity. This represents an important step in a disease in which some organ symptoms get better and others get worse. It is intended to help investigators develop sample size estimates based on meaningful effect sizes and to gauge the clinical relevance of any observed change in disease activity.Medical records from 310 patients drawn from 3 sources were abstracted into a standard format. Each vignette included clinical and laboratory data obtained during 2-3 visits. Ratings on the following 6 instruments were obtained for the same patients during the visit or retrospectively: the British Isles Lupus Assessment Group (BILAG), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the revised Systemic Lupus Activity Measure (SLAM-R), the European Consensus Lupus Activity Measure (ECLAM), the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA)-SLEDAI, and the Responder Index for Lupus Erythematosus (RIFLE). From this pool of vignettes, 5 common vignettes and 10 randomly selected vignettes were rated through a secure Web site by 88 international experts on SLE. The experts, who were blinded to the activity measure scores, were asked to rate each patient's clinical condition as worsened, improved, or unchanged relative to the previous visit. These ratings were transformed by statistical procedures into performance characteristic curves that related a change on a particular SLE activity measure to the physicians' agreement on whether that patient had worsened, improved, or remained the same clinically. These were discussed by the committee members, who were blinded to the actual instrument used. The committee then voted on what level of expert agreement would be used to determine clinically meaningful change.The physician ratings on the 5 common vignettes revealed considerable variation in their clinical appraisals. Overall, the 6 SLE activity measures showed excellent separation of clinical conditions as being worsened, improved, or the same. The committee voted to take 70% agreement by physicians as the point on the performance characteristic curves at which meaningful change in a score could be identified. For each instrument, we computed the units of change required to indicate improvement or worsening.To our knowledge, these are the first response criteria in any disease where a clinically relevant change has been determined a priori and mapped to standardized measures. This criterion should aid the clinical evaluation of new therapies, improve comparability between trials, and facilitate innovative trial designs.

Objective. To determine whether psychosocial factors, chronic diseases, and common geriatric problems are associated with poor physical function 3 years after primary total hip replacement (THR). Methods. We studied a sample of Medicare recipients in Ohio, Pennsylvania, and Colorado (n = 922) who underwent primary THR in 1995 (mean +/- SD age 73.1 +/- 5.6 years, 32% men). Participants completed a questionnaire regarding lifestyle factors, medical history, and quality of life similar to3 years after the surgery. Physical function was measured using the function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index. We assessed the relationship between functional outcome 3 years postsurgery and 4 predictor domains: pain or complications in the operated hip, other musculoskeletal comorbidity, medical factors (obesity, chronic medical comorbidity, rheumatoid arthritis, and such common geriatric problems as falls, poor balance, or incontinence), and psychosocial factors (mental health, regular alcohol consumption, smoking, provider role, living alone, and education). Results. Ten percent of subjects had poor functional status. In a logistic regression model controlling for sex and age, the following factors were associated with an increased risk for poor functional status (in order of importance): pain in the back or lower extremity, severe pain in the operated hip, poor mental health, more than 1 common geriatric problem, obesity, and less than college education. Conclusion. Pain in the operated hip was strongly associated with poor functional status 3 years after THR. However, other factors associated with poor functional status were not related to the hip. Our results suggest that a comprehensive assessment of functional status in elderly THR patients should include assessment of common geriatric problems, mental health status, and weight. (Less)

Background: Vitamin D may improve muscle strength through a highly specific nuclear receptor in muscle tissue. Objectives: We investigated whether there is an association between 25-hydroxyvitamin D [25(OH)D] concentrations and lowerextremity function in ambulatory older persons, whether that association differs by activity level, and, if so, whether there is an identifiable threshold in the association. Design: The study was a population-based survey of the ambulatory US population aged 60 to 90 y( n 4100). Lower-extremity function according to serum 25(OH)D concentrations was assessed by linear regression analyses and regression plots after control for activity level (inactive or active) and several other potential confounders. Separate analyses were performed for the timed 8-foot (ie, 2.4 m) walk test and a repeated sit-to-stand test. Results: The 8-foot walk test compared subjects in the lowest and highest quintiles of 25(OH)D; the latter group had an average decrease of 0.27 s [95% CI: 0.44, 0.09 s (or 5.6%); P for trend 0.001]. The sit-to-stand test compared subjects in the lowest and highest quintiles of 25(OH)D; the latter group had an average decrease of 0.67 s [95% CI: 1.11, 0.23 s (or 3.9%); P for trend 0.017]. In the 25(OH)D reference range of 22.5–94 nmol/L, most of the improvement occurred in subjects with 25(OH)D concentrations between 22.5 and40 nmol/L, and further improvement was seen in the range of 40 –94 nmol/L. Stratification by activity level showed no significant effect modification. Conclusion: In both active and inactive ambulatory persons aged60 y, 25(OH)D concentrations between 40 and 94 nmol/L are associated with better musculoskeletal function in the lower extremities than are concentrations 40 nmol/L. Am J Clin Nutr2004;80:752– 8.

Periodontal disease (PD) is a common chronic inflammatory disease and an important risk factor for tooth loss. Vitamin D might affect periodontal disease risk via an effect on bone mineral density (BMD) or via immunomodulatory effects.The objective was to evaluate whether serum 25-hydroxyvitamin D(3) [25(OH)D(3)] concentrations are associated with PD in the third National Health and Nutrition Examination Survey.We analyzed data on periodontal attachment loss (AL) and serum 25(OH)D(3) concentrations from 11 202 subjects agedor =20 y. Mean AL was modeled in a multiple linear regression with quintile of serum 25(OH)D(3) concentration as an independent variable. The model was stratified by age and sex and was adjusted for age within age groups, race or ethnicity, smoking, diabetes, poverty income ratio, body mass index, estrogen use, and gingival bleeding.25(OH)D(3) concentrations were significantly and inversely associated with AL in men and women agedor =50 y. Compared with men in the highest 25(OH)D(3) quintile, those in the lowest quintile had a mean AL that was 0.39 mm (95% CI: 0.17, 0.60 mm) higher; in women, the difference in AL between the lowest and highest quintiles was 0.26 mm (0.09, 0.43 mm). In men and women younger than 50 y, there was no significant association between 25(OH)D(3) and AL. The BMD of the total femoral region was not associated with AL and did not mediate the association between 25(OH)D(3) and AL.Low serum 25(OH)D(3) concentrations may be associated with PD independently of BMD. Given the high prevalence of PD and vitamin D deficiency, these findings may have important public health implications.

This editorial makes the point that there is now strong evidence that increasing vitamin D intake will lower risk of falling and lower fracture risk in older men and women. There is also strong evidence that higher vitamin D intakes are safe. Currently recommended intakes of vitamin D are insufficient to minimize risk of falling and risk of fracture. The authors of this editorial urge regulatory agencies in the United States and abroad to review the evidence and reassess their dietary recommendations for vitamin D.

Background Care of elderly patients after hip fracture is not well established. Methods We enrolled 173 patients with acute hip fracture who were 65 years or older (79.2% women; mean age, 84 years; 77.4% living at home). Using a factorial design, we randomly allocated patients to extended physiotherapy (PT) (supervised 60 min/d during acute care plus an unsupervised home program) vs standard PT (supervised 30 min/d during acute care plus no home program; single-blinded), and to cholecalciferol therapy, 2000 vs 800 IU/d (double-blinded). Primary outcome was rate of falls; secondary outcome was rate of hospital readmissions during the 12-month follow-up. All analyses included 173 individuals and used multivariate Poisson regression analyses. Results At baseline, 50.9% of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7% of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions. Because this was a factorial design trial, all analyses tested the main effect of each treatment while controlling for the other in 173 participants. Extended vs standard PT reduced the rate of falls by 25% (95% confidence interval [CI], −44% to −1%). Cholecalciferol treatment, 2000 vs 800 IU/d, did not reduce falls (28%; 95% CI, −4% to 68%), but reduced the rate of hospital readmissions by 39% (95% CI, −62% to −1%). Conclusions Extended PT was successful in reducing falls but not hospital readmissions, whereas cholecalciferol treatment, 2000 IU/d, was successful in reducing hospital readmission but not falls. Thus, the 2 strategies may be useful together because they address 2 different and important complications after hip fracture. Trial Registration clinicaltrials.gov identifier:NCT00133640

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 (1α-hydroxyvitamin D 3 (1α-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: v ≥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.

ContextFalls among elderly individuals occur frequently, increase with age, and lead to substantial morbidity and mortality. The role of vitamin D in preventing falls among elderly people has not been well established.ObjectiveTo assess the effectiveness of vitamin D in preventing an older person from falling.Data SourcesMEDLINE and the Cochrane Controlled Trials Register from January 1960 to February 2004, EMBASE from January 1991 to February 2004, clinical experts, bibliographies, and abstracts. Search terms included trial terms: randomized-controlled trial or controlled-clinical trial or random-allocation or double-blind method, or single-blind method or uncontrolled-trials with vitamin D terms: cholecalciferol or hydroxycholecalciferols or calcifediol or dihydroxycholecalciferols or calcitriol or vitamin D/aa[analogs & derivates] or ergocalciferol or vitamin D/bl[blood]; and with accidental falls or falls, and humans.Study SelectionWe included only double-blind randomized, controlled trials (RCTs) of vitamin D in elderly populations (mean age, 60 years) that examined falls resulting from low trauma for which the method of fall ascertainment and definition of falls were defined explicitly. Studies including patients in unstable health states were excluded. Five of 38 identified studies were included in the primary analysis and 5 other studies were included in a sensitivity analysis.Data ExtractionIndependent extraction by 3 authors using predefined data fields including study quality indicators.Data SynthesisBased on 5 RCTs involving 1237 participants, vitamin D reduced the corrected odds ratio (OR) of falling by 22% (corrected OR, 0.78; 95% confidence interval [CI], 0.64-0.92) compared with patients receiving calcium or placebo. From the pooled risk difference, the number needed to treat (NNT) was 15 (95% CI, 8-53), or equivalently 15 patients would need to be treated with vitamin D to prevent 1 person from falling. The inclusion of 5 additional studies, involving 10 001 participants, in a sensitivity analysis resulted in a smaller but still significant effect size (corrected RR, 0.87; 95% CI, 0.80-0.96). Subgroup analyses suggested that the effect size was independent of calcium supplementation, type of vitamin D, duration of therapy, and sex, but reduced sample sizes made the results statistically nonsignificant for calcium supplementation, cholecalciferol, and among men.ConclusionsVitamin D supplementation appears to reduce the risk of falls among ambulatory or institutionalized older individuals with stable health by more than 20%. Further studies examining the effect of alternative types of vitamin D and their doses, the role of calcium supplementation, and effects in men should be considered.

John J. Cannell, MD; Reinhold Vieth, MS, PhD; Walter Willett, MD, DrPH; Michael Zasloff, MD, PhD; John N. Hathcock, MSc, PhD; John H. White, PhD; Sherry A. Tanumihardjo, MSc, PhD; D. Enette Larson-Meyer, PhD; Heike A. Bischoff-Ferrari, MD, MPH; Christel J. Lamberg-Allardt, PhD; Joan M. Lappe, PhD, RN; Anthony W. Norman, PhD; Armin Zittermann, PhD; Susan J. Whiting, MSc, PhD; William B. Grant, PhD; Bruce W. Hollis, PhD; Edward Giovannucci, MD

Besides its well-known effect on bone metabolism, recent researches suggest that vitamin D may also play a role in the muscular, immune, endocrine, and central nervous systems. Double-blind RCTs support vitamin D supplementation at a dose of 800 IU per day for the prevention of falls and fractures in the senior population. Ecological, case–control and cohort studies have suggested that high vitamin D levels were associated with a reduced risk of autoimmune diseases, type 2 diabetes, cardio-vascular diseases and cancer but large clinical trials are lacking today to provide solid evidence of a vitamin D benefit beyond bone health. At last, the optimal dose, route of administration, dosing interval and duration of vitamin D supplementation at a specific target dose beyond the prevention of vitamin D deficiency need to be further investigated.