Similarities and differences between patients included and excluded from a randomized clinical trial of vitamin d supplementation for improving glucose tolerance in prediabetes: interpreting broader applicability

BACKGROUND: Randomized Clinical Trial (RCT) designs range from highly selective resulting in lack of external validity to more inclusive, requiring large sample sizes to observe significant results. Few publications, however, have compared excluded to enrolled participants. We aimed to assess our trial’s design based on the effectiveness versus efficacy continuum using the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool and to compare included and excluded patients. METHODS: Fifteen members of endocrinology section completed PRECIS for DIVA (D-Vitamin Intervention in VA) trial; an RCT evaluating vitamin D supplementation in improving dysglycemia in patients with prediabetes. Retrospective chart review compared subjects excluded (OUT) to those included (IN) in RCT. Student’s t and Chi-square tests were used to compare continuous and categorical variables. Additionally, multiple logistic regression was completed. RESULTS: PRECIS scores were nearly universally pragmatic. 178 patients enrolled in DIVA trial were compared with 178 randomly selected patients excluded from study involvement. There was no significant difference between IN and OUT for the majority of the continuous and all of the categorical variables. Multivariate logistic regression identified only the A1c, HDL and Charlson Index as significant predictors of a participant’s inclusion or exclusion. There was higher HDL (51.3(13.9) versus 44.6(10.1), P = 0.001) and Charlson Index (2.85(1.6) versus 2.2(1.17), P = 0.001) for OUT versus IN groups. Subanalysis of excluded patients in A1c range 5.7 to 6.9, had lower BMI (30.7(3.4) versus 32(2.7), P = 0.002) but higher HDL (mg/l: 49.7(11.8) versus 44.6(10.1), P = 0.001) and Charlson index (2.85(1.6) versus 2.2(1.17), P = 0.001) than included participants. Additionally, there was a trend towards higher rates of cancer (22.9 % versus 12.9 %, P = 0.033) but less psychiatric problems (56.2 % versus 72.5 %, P = 0.026) and thiazide diuretic use (18.1 % versus 29.8 %, P = 0.034). CONCLUSION: DIVA trial design appears to favor broad clinical applicability. The majority of objectively compared variables did not different between patients included and excluded from this RCT. Advice based on the evidence from this RCT may be applicable to a larger group of patients than those fitting inclusion/exclusion criteria alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT01375660 (registered 15 June 2011). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0812-0) contains supplementary material, which is available to authorized users

The prevalence of and risk factors for radiographic vertebral fractures in older Indian women and men: Delhi Vertebral Osteoporosis Study (DeVOS)

Summary: High prevalence of vertebral fractures (17.9% over all; 18.8% male and 17.1% female) was observed in 808 free-living residents of Delhi, India, aged more than 50 years. The prevalence rates were comparable to that reported in Caucasian populations. While there was an increase in fracture prevalence with age in females, the same was not observed in males. Introduction: The aim of this paper is to study the prevalence of and risk factors for morphometric vertebral fractures in elderly Indian men and women over 50 years of age. Methods: We recruited 808 healthy subjects aged 50 years or more, residing in three residential colonies in Delhi, India who voluntarily agreed to participate in this study. All subjects underwent lateral X-rays of the lumbar and thoracic spine according to a standardized protocol. All X-rays were blindly evaluated by a single trained person using an advanced semi-automated software (Optasia Medical) based on Genant’s semiquantitative method. Recruited subjects underwent anthropometric, biochemical and hormonal evaluation. Results: With a mean age of 64.9 (±6.7) years, 345 males and 415 females were evaluated. Vertebral fractures were present in 17.9% (95% CI 15.2, 20.6) subjects [males, 18.8% (95% CI 14.6, 23), females 17.1% (95% CI 13.5, 20.8)]. Prevalence of vertebral fractures increased with age in females from 14.7% in 50–59 years age group to 22.4% in those ≥70 years, but not in men. Overweight subjects had significantly lower risk [OR, 0.63 (95% CI 0.41, 0.97), p = 0.035] of vertebral fractures. Serum 25 hydroxyvitamin D levels, intake of calcium and vitamin D or history of previous fractures were not statistically different between patients with or without prevalent vertebral fractures. Conclusions: The prevalence of vertebral fractures among older Indians was comparable to that reported in Caucasian populations. Prevalence of vertebral fractures increased with age in females, but not in males. Overweight individuals were protected against vertebral fractures

Relationship between BMD and prevalent vertebral fractures in Indian women older than 50 yr

The purpose of the study was to study the relationship of morphometric vertebral fractures with Bone Mineral Density (BMD) in Indian women older than 50 yr. Four hundred fifteen healthy Indian women older than 50 yr (mean age: 62.8 yr) underwent lateral X-rays of the lumbar and thoracic spine. Genant's semiquantitative method was used to diagnose and classify morphometric vertebral fractures. BMD was measured by DXA at lumbar spine and total hip. Recruited subjects underwent anthropometric, biochemical, and hormonal evaluation. Vertebral fractures were present in 17.1% (95% confidence interval: 13.5, 20.8) subjects. Prevalence of osteoporosis based on BMD was 35.7%. By adding those with prevalent fractures, the number of women requiring therapy for osteoporosis would increase to 46.5%. The BMD measured at femur neck, total hip and lumbar spine (L1eL4) was not found to be lower in women with vertebral fractures as compared with those without fractures. BMD was not found to be lower in women with vertebral fractures as compared with those without fractures. Significant number of additional subjects with BMD in the normal or osteopenic range become eligible for osteoporosis treatment when presence of vertebral fracture is used as an independent indication for such treatment

The Indian Society for Bone and Mineral Research (ISBMR) position statement for the diagnosis and treatment of osteoporosis in adults

The Indian Society for Bone and Mineral Research (ISBMR) has herein drafted clinical practice guidelines for the diagnosis and management of osteoporosis for the people of India. Implementation of the position statement in clinical practice is expected to improve the overall care of patients with osteoporosis in India. PURPOSE: In India, osteoporosis is a major public health problem. However, in the absence of any robust regional guidelines, the screening, treatment, and follow-up of patients with osteoporosis are lagging behind in the country. METHODS: The Indian Society for Bone and Mineral Research (ISBMR), which is a multidisciplinary group of physicians, researchers, dietitians, and epidemiologists and who study bone and related tissues, in their annual meeting, drafted the guidelines for the diagnosis and management of osteoporosis that would be appropriate in a resource constraint setting like India. RESULTS: Diagnosis of osteoporosis can be made in a patient with minimal trauma fracture without the aid of any other diagnostic tools. In others, bone mineral density measured by dual-energy X-ray absorptiometry remains the modality of choice. Data indicates that osteoporotic fractures occur at an earlier age in Indians than in the West; hence, screening for osteoporosis should begin at an earlier age. FRAX can be used for fracture risk estimation; however, it may underestimate the risk of future fractures in our population and still needs validation. Maintaining optimum serum 25-hydroxyvitamin D levels is essential, which, in most cases, would require regular vitamin D supplementation. Pharmacotherapy should be guided by the presence/absence of vertebral/hip fractures or the severity of risk based on clinical factors, although bisphosphonates remain the first choice in most cases. Regular follow-up is essential to ensure adherence and response to therapy. CONCLUSIONS: Implementation of the position statement in clinical practice is expected to improve the overall care of patients with osteoporosis in India