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Journal of Bone and Mineral Research :... Apr 2019Meta-analyses conducted >15 years ago reported that improvements in bone mineral density (BMD) were associated with reduction in vertebral and nonvertebral fractures in... (Meta-Analysis)
Meta-Analysis
Meta-analyses conducted >15 years ago reported that improvements in bone mineral density (BMD) were associated with reduction in vertebral and nonvertebral fractures in osteoporosis trials. Numerous studies have been conducted since then, incorporating new therapies with different mechanisms of action and enrolling many more subjects. To extend these prior analyses, we conducted a meta-regression of 38 placebo-controlled trials of 19 therapeutic agents to determine the association between improvements in BMD and reductions in fracture risk. We used a linear model to examine the relationship between mean percent difference in BMD change between treatment and placebo groups and the logarithm of the relative risk. We found that greater improvements in BMD were strongly associated with greater reductions in vertebral and hip fractures but not nonvertebral fractures. For vertebral fracture, the r values for total hip, femoral neck, and lumbar spine BMD change were 0.56, 0.54, and 0.63, respectively (p ≤ 0.0002). For a 2% or 6% improvement in total hip BMD, we might expect a 28% or 66% reduction, respectively, in vertebral fracture risk. For hip fracture, the r values for total hip, femoral neck, and lumbar spine BMD change were 0.48 (p = 0.01), 0.42 (p = 0.02), and 0.22 (ns), respectively. For a 2% or 6% improvement in total hip BMD, we might expect a 16% or 40% reduction in hip fracture risk. In conclusion, our results extend prior observations that larger improvements in dual-energy X-ray absorptiometry (DXA)-based BMD are associated with greater reductions in fracture risk, particularly for vertebral and hip fractures. Although these results cannot be directly applied to predict the treatment benefit in an individual patient, they provide compelling evidence that improvements in BMD with osteoporosis therapies may be useful surrogate endpoints for fracture in trials of new therapeutic agents. © 2019 American Society for Bone and Mineral Research.
Topics: Absorptiometry, Photon; Bone Density; Hip Fractures; Humans; Osteoporosis; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Risk Factors; Spinal Fractures
PubMed: 30674078
DOI: 10.1002/jbmr.3641 -
The Cochrane Database of Systematic... Jan 2023Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and... (Review)
Review
BACKGROUND
Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life.
OBJECTIVES
To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search was 12 April 2022.
SELECTION CRITERIA
We included randomised controlled trials in healthy premenopausal women (with or without calcium or vitamin D deficiency) comparing supplementation of calcium or vitamin D (or both) at any dose and by any route of administration versus placebo for at least three months. Vitamin D could have been administered as cholecalciferol (vitamin D) or ergocalciferol (vitamin D).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Outcomes included total hip bone mineral density (BMD), lumbar spine BMD, quality of life, new symptomatic vertebral fractures, new symptomatic non-vertebral fractures, withdrawals due to adverse events, serious adverse events, all reported adverse events and additional withdrawals for any reason.
MAIN RESULTS
We included seven RCTs with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Mean age ranged from 18.1 to 42.1 years. Studies reported results for total hip or lumbar spine BMD (or both) and withdrawals for various reasons, but none reported fractures or withdrawals for adverse events or serious adverse events. Results for the reported outcomes are presented for the three comparisons: calcium versus placebo, vitamin D versus placebo, and calcium plus vitamin D versus placebo. In all comparisons, there was no clinical difference in outcomes, and the certainty of the evidence was moderate to low. Most studies were at risk of selection, performance, detection, and reporting biases. Calcium versus placebo Four studies compared calcium versus placebo (138 participants in the calcium group and 123 in the placebo group) with mean ages from 18.0 to 47.3 years. Calcium supplementation may have little to no effect on total hip or lumbar spine BMD after 12 months in three studies and after six months in one study (total hip BMD: mean difference (MD) -0.04 g/cm, 95% confidence interval (CI) -0.11 to 0.03; I = 71%; 3 studies, 174 participants; low-certainty evidence; lumbar spine BMD: MD 0 g/cm, 95% CI -0.06 to 0.06; I = 71%; 4 studies, 202 participants; low-certainty evidence). Calcium alone supplementation does not reduce or increase the withdrawals in the trials (risk ratio (RR) 0.78, 95% CI 0.52 to 1.16; I = 0%; 4 studies, 261 participants: moderate-certainty evidence). Vitamin D versus placebo Two studies compared vitamin D versus placebo (110 participants in the vitamin D group and 79 in the placebo group), with mean ages from 18.0 to 32.7 years. These studies reported lumbar spine BMD as a mixture of MDs and percent of change and we were unable to pool the results. In the original studies, there were no differences in lumbar BMD between groups. Vitamin D alone supplementation does not reduce or increase withdrawals for any reason between groups (RR 0.74, 95% CI 0.46 to 1.19; moderate-certainty evidence). Calcium plus vitamin D versus placebo Two studies compared calcium plus vitamin D versus placebo (271 participants in the calcium plus vitamin D group and 270 in the placebo group; 220 participants from Woo 2007 and 50 participants from Islam 2010). The mean age range was 18.0 to 36 years. These studies measured different anatomic areas, one study reported total hip BMD and the other study reported lumbar spine BMD; therefore, data were not pooled for this outcome. The individual studies found no difference between groups in percent of change on total hip BMD (-0.03, 95% CI -0.06 to 0; moderate-certainty evidence), and lumbar spine BMD (MD 0.01, 95% CI -0.01 to 0.03; moderate-certainty evidence). Calcium plus vitamin D supplementation may not reduce or increase withdrawals for any reason (RR 0.82, 95% CI 0.29 to 2.35; I = 72%; 2 studies, 541 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non-vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful.
Topics: Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Vitamin D; Calcium; Bone Density; Quality of Life; Vitamins; Calcium, Dietary; Osteoporosis; Fractures, Bone; Cholecalciferol; Randomized Controlled Trials as Topic
PubMed: 36705288
DOI: 10.1002/14651858.CD012664.pub2 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2016To analyze articles that studied patients submitted to diphosphonates therapy and who received dental implants before, during or after bisphosphonate (BP) treatment,... (Review)
Review
BACKGROUND
To analyze articles that studied patients submitted to diphosphonates therapy and who received dental implants before, during or after bisphosphonate (BP) treatment, compared to healthy patients, analyzing the increase of failure and loss of implants or bisphosphonate related osteonecrosis of the jaw (BRONJ) incidence.
MATERIAL AND METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was used in this study. The clinical question in "PICO" format was: In patients under bisphosphonate therapy, do dental implants placement, compared to healthy patients, increase the failure and loss of implants or bisphosphonate related osteonecrosis of the jaw incidence? PubMed/MEDLINE was searched for articles published up until April 15, 2015 using a combination of MeSH terms and their Entry terms.
RESULTS
The search resulted in 375 articles. After selection according to the eligibility criteria, 15 studies fulfilled were included (eight retrospective, one prospective and six case series), with a total of 1339 patients analyzed, 3748 implants placed, 152 loss of implants and 78 cases of BRONJ.
CONCLUSIONS
Due to the lack of randomized clinical trials looking at this theme, further studies with longer follow-up are needed to elucidate the remaining questions. Thus, it is wise to be careful when planning dental implant surgery in patients undergoing bisphosphonate therapy because of the risk of developing BRONJ as well as occurring failure of implant. Moreover, complete systemic condition of the patient must be also taking into considering when such procedures are performed.
Topics: Bone Density Conservation Agents; Dental Implants; Diphosphonates; Humans; Prospective Studies; Retrospective Studies
PubMed: 27475681
DOI: 10.4317/medoral.20920 -
Annals of African Medicine 2019The overall success of dental implants depends on the crestal bone support around the implants. During the initial years of dental implant placement, the bone loss...
BACKGROUND
The overall success of dental implants depends on the crestal bone support around the implants. During the initial years of dental implant placement, the bone loss around the implants determines the success rate of treatment. Platform switching (PLS) concept preserves the crestal bone loss, and this approach should be applied clinically for the overall success of dental implants.
PURPOSE
The purpose of this study is to discuss the literature dealing with the concept of PLS concept and preservation of marginal bone, the mechanism by which it contributes to maintenance of marginal bone, its clinical applications, advantages, and disadvantages, to assess its survival rates.
MATERIALS AND METHODS
PubMed and Google Scholar search was done to find out the studies involving PLS concept from 2005 to 2017. Data were analyzed using SPSS statistical software.
RESULTS
Literature search revealed studies involving concepts of PLS, comparison of platform-switched and nonplatform-switched implants, case reports on PLS, and studies with histological and finite element analyses regarding PLS.
CONCLUSION
PLS helps preserve crestal bone around the implants, and this concept should be followed when clinical situations in implant placement permit.
Topics: Adult; Alveolar Bone Loss; Alveolar Process; Bone Density; Dental Abutments; Dental Implant-Abutment Design; Dental Implantation; Dental Implants; Dental Prosthesis Design; Humans; Prosthesis Fitting
PubMed: 30729925
DOI: 10.4103/aam.aam_15_18 -
BMJ (Clinical Research Ed.) Sep 2015To examine the evidence underpinning recommendations to increase calcium intake through dietary sources or calcium supplements to prevent fractures. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To examine the evidence underpinning recommendations to increase calcium intake through dietary sources or calcium supplements to prevent fractures.
DESIGN
Systematic review of randomised controlled trials and observational studies of calcium intake with fracture as an endpoint. Results from trials were pooled with random effects meta-analyses.
DATA SOURCES
Ovid Medline, Embase, PubMed, and references from relevant systematic reviews. Initial searches undertaken in July 2013 and updated in September 2014.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials or cohort studies of dietary calcium, milk or dairy intake, or calcium supplements (with or without vitamin D) with fracture as an outcome and participants aged >50.
RESULTS
There were only two eligible randomised controlled trials of dietary sources of calcium (n=262), but 50 reports from 44 cohort studies of relations between dietary calcium (n=37), milk (n=14), or dairy intake (n=8) and fracture outcomes. For dietary calcium, most studies reported no association between calcium intake and fracture (14/22 for total, 17/21 for hip, 7/8 for vertebral, and 5/7 for forearm fracture). For milk (25/28) and dairy intake (11/13), most studies also reported no associations. In 26 randomised controlled trials, calcium supplements reduced the risk of total fracture (20 studies, n=58,573; relative risk 0.89, 95% confidence interval 0.81 to 0.96) and vertebral fracture (12 studies, n=48,967. 0.86, 0.74 to 1.00) but not hip (13 studies, n=56,648; 0.95, 0.76 to 1.18) or forearm fracture (eight studies, n=51,775; 0.96, 0.85 to 1.09). Funnel plot inspection and Egger's regression suggested bias toward calcium supplements in the published data. In randomised controlled trials at lowest risk of bias (four studies, n=44,505), there was no effect on risk of fracture at any site. Results were similar for trials of calcium monotherapy and co-administered calcium and vitamin D. Only one trial in frail elderly women in residential care with low dietary calcium intake and vitamin D concentrations showed significant reductions in risk of fracture.
CONCLUSIONS
Dietary calcium intake is not associated with risk of fracture, and there is no clinical trial evidence that increasing calcium intake from dietary sources prevents fractures. Evidence that calcium supplements prevent fractures is weak and inconsistent.
Topics: Aged; Bone Density; Calcium, Dietary; Dietary Supplements; Fractures, Bone; Frail Elderly; Humans; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 26420387
DOI: 10.1136/bmj.h4580 -
Environmental Health : a Global Access... Nov 2022Exposure to endocrine disruptors, such as phthalates, may impact bone mineral density (BMD) through a variety of mechanisms. Studies of phthalate exposure and BMD in... (Review)
Review
BACKGROUND
Exposure to endocrine disruptors, such as phthalates, may impact bone mineral density (BMD) through a variety of mechanisms. Studies of phthalate exposure and BMD in humans are scarce.
OBJECTIVES
To synthesize published data on the association between phthalate metabolites and BMD in humans and to provide methodological suggestions for future research.
METHODS
A single investigator searched PubMed for relevant studies, including observational studies of phthalate exposure and BMD in children and postmenopausal women. Twelve studies were screened with 5 meeting the eligibility criteria and included for review. A quality assessment form was used as a quality measure and key information was extracted from the included studies.
RESULTS
In one prospective study among postmenopausal women, higher levels of monocarboxyoctyl phthalate (MCOP) and monocarboxynonyl phthalate (MCNP) were significantly associated with lower BMD among nonusers of hormone therapy (HT). In cross-sectional studies of postmenopausal women, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono (3-carboxypropyl) phthalate (MCPP), and mono-benzyl phthalate (MBzP) were negatively associated with BMD, and MCNP was positively associated with BMD, but these results were not replicated across studies. In studies of fetal exposure to phthalates and childhood BMD, significant positive associations between MCPP and BMD in children at age 12 years were found in 1 study, while associations were null in the other study.
CONCLUSIONS
Studies among postmenopausal women provide suggestive evidence of an association between urinary phthalate metabolite concentration and decreased BMD. Results from studies of childhood BMD are inconclusive given the limited data and their limitations. More research is needed to address limitations and further investigate the association between phthalate exposure and human BMD.
Topics: Child; Female; Humans; Bone Density; Environmental Pollutants; Cross-Sectional Studies; Prospective Studies; Phthalic Acids; Environmental Exposure
PubMed: 36369032
DOI: 10.1186/s12940-022-00920-5 -
Bone Jan 2022Magnesium plays a key role in bone health and may, therefore, represent an interesting nutrient for the prevention of bone loss and osteoporosis. The aim of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Magnesium plays a key role in bone health and may, therefore, represent an interesting nutrient for the prevention of bone loss and osteoporosis. The aim of this systematic review and meta-analysis was to investigate the impact of magnesium intake from any source on bone mineral density (BMD), bone mineral content (BMC), bone turnover markers, and fracture risk in older adults.
METHODS
A systematic search was conducted using Embase, Medline Ovid and Cochrane Central from database inception to October 2020. All studies that related magnesium intake with bone health outcomes among adults aged ≥60 years were included. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias assessments. Authors were contacted for missing data.
RESULTS
Once 787 records were screened, six cohort studies, one case-control study and five cross-sectional studies were included. Qualitative evaluation demonstrated a positive trend between higher magnesium intake and higher hip and femoral neck BMD. Meta-analysis of four studies showed a significant positive association between magnesium intake and hip BMD (pooled beta: 0.03, 95% CI: 0.01-0.06, p < 0.05).
CONCLUSIONS
This systematic review indicates that a higher magnesium intake may support an increase in hip and femoral neck BMD. Due to limited research no associations with BMD at other sites or fractures were found. There is a need for properly designed cohort studies to determine the association between magnesium intake and bone health in older adults. Next, large and long-term randomized controlled trials in older adults are needed to determine whether an increase in magnesium (supplementation) intake can improve bone health. The combination of several bone nutrients (calcium, vitamin D, protein, magnesium and potentially more) may be needed for the most optimal effect on bone health and to delay or prevent the development of osteoporosis.
Topics: Aged; Bone Density; Case-Control Studies; Cross-Sectional Studies; Humans; Magnesium; Middle Aged; Osteoporosis
PubMed: 34666201
DOI: 10.1016/j.bone.2021.116233 -
Cureus Feb 2023Postmenopausal osteoporosis is a chronic condition with decreased bone mass and altered bone structure, leading to a greater risk of fractures among older women.... (Review)
Review
Postmenopausal osteoporosis is a chronic condition with decreased bone mass and altered bone structure, leading to a greater risk of fractures among older women. Exercise has been proposed as a potentially effective non-pharmacological method to prevent this condition. In this systematic review, we investigate the effects and safety of high-impact and high-intensity exercises in improving bone density at popular sites of fragility fractures, namely, the hip and spine. This review also highlights the mechanism of these exercises in improving bone density and other aspects of bone health in postmenopausal women. This study is done adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After applying the eligibility criteria, we selected 10 articles from PubMed and Google Scholar to be included in our study. Based on the findings from the studies, we established that high-intensity and high-impact exercises are effective in improving, or at the very least maintaining, bone density in the lumbar spine and femur in postmenopausal women. An exercise protocol including high-intensity resistance exercises and high-impact training is shown to be most effective in improving bone density and other parameters of bone health. These exercises were found to be safe in older women, however, careful supervision is recommended. All limitations considered, high-intensity and high-impact exercises are an effective strategy to enhance bone density, and potentially reduce the burden of fragility as well as compression fractures in postmenopausal women.
PubMed: 36895528
DOI: 10.7759/cureus.34644 -
Nutrition Reviews Apr 2021Consumption of yogurt and other fermented products is associated with improved health outcomes. Although dairy consumption is included in most dietary guidelines, there...
Consumption of yogurt and other fermented products is associated with improved health outcomes. Although dairy consumption is included in most dietary guidelines, there have been few specific recommendations for yogurt and cultured dairy products. A qualitative systematic review was conducted to determine the effect of consumption of fermented milk products on gastrointestinal and cardiovascular health, cancer risk, weight management, diabetes and metabolic health, and bone density using PRISMA guidelines. English language papers in PubMed were searched, with no date restrictions. In total, 1057 abstracts were screened, of which 602 were excluded owing to lack of appropriate controls, potential biases, and experimental design issues. The remaining 455 papers were independently reviewed by both authors and 108 studies were included in the final review. The authors met regularly to concur, through consensus, on relevance, methods, findings, quality, and conclusions. The included studies were published between 1979 and 2017. From the 108 included studies, 76 reported a favorable outcome of fermented milks on health and 67 of these were considered to be positive or neutral quality according to the Academy of Nutrition and Dietetics' Quality Criteria Checklist. Of the 32 remaining studies, the study outcomes were either not significant (28) or unfavorable (4), and most studies (18) were of neutral quality. A causal relationship exists between lactose digestion and tolerance and yogurt consumption, and consistent associations exist between fermented milk consumption and reduced risk of breast and colorectal cancer and type 2 diabetes, improved weight maintenance, and improved cardiovascular, bone, and gastrointestinal health. Further, an association exists between prostate cancer occurrence and dairy product consumption in general, with no difference between fermented and unfermented products. This article argues that yogurt and other fermented milk products provide favorable health outcomes beyond the milk from which these products are made and that consumption of these products should be encouraged as part of national dietary guidelines. Systematic review registration: PROSPERO registration no. CRD42017068953.
Topics: Animals; Bone Density; Breast Neoplasms; Colorectal Neoplasms; Cultured Milk Products; Diabetes Mellitus, Type 2; Eating; Female; Humans; Lactose; Male; Neoplasms; Prostatic Neoplasms; Risk; Yogurt
PubMed: 32447398
DOI: 10.1093/nutrit/nuaa013 -
Evidence Report/technology Assessment Aug 2007To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children,... (Review)
Review
OBJECTIVES
To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children, women of reproductive age, postmenopausal women and elderly men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on bone mineral density (BMD) and fracture or fall risk; and the identification of potential harms of vitamin D above current reference intakes.
DATA SOURCES
MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February 2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006).
REVIEW METHODS
Two independent reviewers completed a multi-level process of screening the literature to identify eligible studies (title and abstract, followed by full text review, and categorization of study design per key question). To minimize bias, study design was limited to randomized controlled trials (RCTs) wherever possible. Study criteria for question one were broadened to include observational studies due to a paucity of available RCTs, and question four was restricted to systematic reviews to limit scope. Data were abstracted in duplicate and study quality assessed. Differences in opinion were resolved through consensus or adjudication. If clinically relevant and statistically feasible, meta-analyses of RCTs on vitamin D supplementation and bone health outcomes were conducted, with exploration of heterogeneity. When meta-analysis was not feasible, a qualitative systematic review of eligible studies was conducted.
RESULTS
167 studies met our eligibility criteria (112 RCTs, 19 prospective cohorts, 30 case-controls and six before-after studies). The largest body of evidence on vitamin D status and bone health was in older adults with a lack of studies in premenopausal women and infants, children and adolescents. The quality of RCTs was highest in the vitamin D efficacy trials for prevention of falls and/or fractures in older adults. There was fair evidence of an association between low circulating 25(OH)D concentrations and established rickets. However, the specific 25(OH)D concentrations associated with rickets is uncertain, given the lack of studies in populations with dietary calcium intakes similar to North American diets and the different methods used to determine 25(OH)D concentrations. There was inconsistent evidence of an association of circulating 25(OH)D with bone mineral content in infants, and fair evidence that serum 25(OH)D is inversely associated with serum PTH. In adolescents, there was fair evidence for an association between 25(OH)D levels and changes in BMD. There were very few studies in pregnant and lactating women, and insufficient evidence for an association between serum 25(OH)D and changes in BMD during lactation, and fair evidence of an inverse correlation with PTH. In older adults, there was fair evidence that serum 25(OH)D is inversely associated with falls, fair evidence for a positive association with BMD, and inconsistent evidence for an association with fractures. The imprecision of 25(OH)D assays may have contributed to the variable thresholds of 25(OH)D below which the risk of fractures, falls or bone loss was increased. There was good evidence that intakes from vitamin D-fortified foods (11 RCTs) consistently increased serum 25(OH)D in both young and older adults. Eight randomized trials of ultraviolet (UV)-B radiation (artificial and solar exposure) were small and heterogeneous with respect to determination of the exact UV-B dose and 25(OH)D assay but there was a positive effect on serum 25(OH)D concentrations. It was not possible to determine how 25(OH)D levels varied by ethnicity, sunscreen use or latitude. Seventy-four trials examined the effect of vitamin D(3) or D(2) on 25(OH)D concentrations. Most trials used vitamin D(3), and the majority enrolled older adults. In three trials, there was a greater response of serum 25(OH)D concentrations to vitamin D(3) compared to vitamin D(2), which may have been due to more rapid clearance of vitamin D(2) in addition to other mechanisms. Meta-analysis of 16 trials of vitamin D(3) was consistent with a dose-response effect on serum 25(OH)D when comparing daily doses of <400 IU to doses >/= 400 IU. An exploratory analysis of the heterogeneity demonstrated a significant positive association comparable to an increase of 1 - 2 nmol/L in serum 25(OH)D for every 100 additional units of vitamin D although heterogeneity remained after adjusting for dose. Vitamin D(3) in combination with calcium results in small increases in BMD compared to placebo in older adults although quantitative synthesis was limited due to variable treatment durations and BMD sites. The evidence for fracture reduction with vitamin D supplementation was inconsistent across 15 trials. The combined results of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg) was consistent with a benefit on fractures although in a subgroup analysis by setting, benefit was primarily in elderly institutionalized women (fair evidence from two trials). There was inconsistent evidence across 14 RCTs of a benefit on fall risk. However, a subgroup analysis showed a benefit of vitamin D in postmenopausal women, and in trials that used vitamin D(3) plus calcium. In addition, there was a reduction in fall risk with vitamin D when six trials that adequately ascertained falls were combined. Limitations of the fall and fracture trials included poor compliance with vitamin D supplementation, incomplete assessment of vitamin D status and large losses to follow-up. We did not find any systematic reviews that addressed the question on the level of sunlight exposure that is sufficient to maintain serum 25(OH)D concentrations but minimizes risk of melanoma and non-melanoma skin cancer. There is little evidence from existing trials that vitamin D above current reference intakes is harmful. In most trials, reports of hypercalcemia and hypercalciuria were not associated with clinically relevant events. The Women's Health Initiative study did report a small increase in kidney stones in postmenopausal women aged 50 to 79 years whose daily vitamin D(3) intake was 400 IU (the reference intake for 50 to 70 years, and below the reference intake for > 70 years) combined with 1000 mg calcium. The increase in renal stones corresponded to 5.7 events per 10,000 person-years of exposure. The women in this trial had higher calcium intakes than is seen in most post-menopausal women.
CONCLUSIONS
The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.
Topics: Adolescent; Aged; Bone Density; Bone Density Conservation Agents; Bone and Bones; Child; Child, Preschool; Dietary Supplements; Female; Fractures, Bone; Humans; Infant; Lactation; Male; Osteoporosis, Postmenopausal; Pregnancy; Rickets; Sunlight; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency
PubMed: 18088161
DOI: No ID Found