Effects of intermittent overload doses of oral vitamin D3 on serum 25(OH)D concentrations and the incidence rates of fractures, falls, and mortality in elderly individuals: A systematic review and meta-analysis.

Vitamin D is commonly used to prevent and treat osteoporosis, with studies indicating its potential to reduce fractures, falls, and mortality. However, meta-analyses present inconsistent findings regarding its efficacy, particularly reflecting significant variability in data and outcomes related to various dosing regimens. In this meta-analysis, we assessed the impact of high-dose intermittent oral administration of vitamin D3 on serum 25(OH)D levels, fractures, falls, and mortality among elderly individuals. We included 14 randomized controlled trials (RCTs) and employed Review Manager 5.4 for statistical analysis. Our findings indicate that intermittent monthly administration of vitamin D3 (over 800 IU per day) significantly raised serum 25(OH)D levels at all timepoints after six months, maintaining levels above 75 nmol/L throughout the year. This regimen showed no increase in all-cause mortality, with a risk ratio (95% CI) of 0.95 (0.87-1.04). Likewise, it did not significantly reduce the risks of falls and fractures, with risk ratios of 1.02 (0.98-1.05) and 0.95 (0.87-1.04) respectively. Although one-year intermittent administration significantly increased the concentration of 25(OH)D in serum, further research is needed to determine if this method would increase the incidence of falls. Therefore, it is not recommended at this stage due to the lack of demonstrated safety in additional relevant RCTs. This study had been registered at PROSPERO (CRD42022363229).

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.

Risk of Bone Fracture on Vegetarian and Vegan Diets.

PURPOSE OF REVIEW: Bone fractures can have a devastating effect on health, especially in the elderly, undermining their independence for daily activities, and increasing the risk of comorbidities and mortality. Nutrition is a key factor in maintaining an optimal bone health across the lifespan. The number of people that choose to avoid meat or even all animal products is increasing globally, for a diversity of reasons. Properly planned vegetarian and vegan diets are widely recognized as a healthy dietary pattern, but the long-term impact of these diets on bone health and more specifically risk of bone fractures is less clear. Classic studies have observed a slightly lower bone mineral density in vegetarians but have many limitations, including inadequate adjusting for relevant confounding factors, and cross-sectional design. The aim of this review is to summarize and put into context the current evidence on the effect of vegetarian and vegan diets on bone health, with a focus on fracture risk. RECENT FINDINGS: In recent years, results from many large prospective studies have emerged, which allowed us to assess the risk of incident bone fractures in vegetarians. In these studies, vegetarian and especially vegan diets were associated with an increased risk of bone fractures. In many recent prospective cohort studies, vegetarian and especially vegan diets were associated with an increased risk of bone fractures. At least part of this risk could be due to a lower body mass index and a lower intake of nutrients such as calcium, vitamin D, and protein. Some evidence suggests that combined vitamin D and calcium supplementation and other factors such as consumption of protein-rich foods may attenuate this risk. The eventual deleterious effect of vegetarian diets on bone health should be contextualized and balanced with its benefits, such as lower risk of cardiovascular disease and cancer.

Maternal Diet Associates with Offspring Bone Mineralization, Fracture Risk and Enamel Defects in Childhood and Influences the Prenatal Effect of High-Dose Vitamin D Supplementation.

We previously demonstrated a beneficial effect of high-dose vitamin D in pregnancy on offspring bone and dental health. Here, we investigated the effect of maternal dietary patterns during pregnancy on the risk of bone fractures, bone mineralization and enamel defects until age 6 years in the offspring. Further, the influence of diet on the effect of high-dose vitamin D was analyzed in the COPSAC2010 mother-child cohort including 623 mother-child pairs. A weighted network analysis on FFQs revealed three specific maternal dietary patterns that associated (Bonferroni p < 0.05) with both offspring bone and dental health. The effect of prenatal high-dose (2800 IU/day) vs. standard-dose (400 IU/day) vitamin D on offspring bone mineral content (adjusted mean difference (aMD): 33.29 g, 95% CI: 14.48-52.09, p < 0.001), bone mineral density (aMD: 0.02 g/cm2 (0.01-0.04), p < 0.001), fracture risk (adjusted incidence rate ratio: 0.36 (0.16-0.84), p = 0.02), and enamel defects in primary (adjusted odds ratio (aOR): 0.13 (0.03-0.58), p < 0.01) and permanent molars (aOR: 0.25; (0.10-0.63), p < 0.01) was most pronounced when mothers had lower intake of fruit, vegetables, meat, eggs, sweets, whole grain, offal and fish. This study suggests that prenatal dietary patterns influence offspring bone and dental development, and should be considered in order to obtain the full benefits of vitamin D to enhance personalized supplementation strategy.

Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Vitamin D supplementation has been shown to increase total hip areal bone mineral density in healthy children and adolescents. We aimed to investigate whether supplementing schoolchildren living in Mongolia with weekly vitamin D3 for 3 years affected fracture risk. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled trial across 18 public schools in Ulaanbaatar, Mongolia. Schoolchildren were eligible if they were aged 6-13 years at screening, had a negative QuantiFERON-TB Gold In-tube assay (QFT) result, were not hypersensitive to vitamin D or immunocompromised, did not use vitamin D supplements, did not have clinical signs of rickets, and had no intention of leaving Ulaanbaatar within 3 years. Participants were randomly assigned (1:1) to receive either vitamin D (oral dose of 14 000 international units [IU] vitamin D3, once per week) or placebo for 3 years using permuted block randomisation stratified by school of attendance. Participants, care providers, and all trial staff were masked to group assignment during the intervention. Prespecified secondary outcomes were incidence of fractures and adverse events, ascertained using questionnaires. The fracture and safety analyses included participants who completed at least one follow-up fracture questionnaire. We estimated adjusted risk ratios (RRs) and 95% CIs using generalised linear models with binomial distribution and a log link function with adjustment for school of attendance. The trial is registered with ClinicalTrials.gov, NCT02276755, and the intervention ended in May, 2019. FINDINGS: Between Sept 2, 2015, and March 20, 2017, 11 475 children were invited to participate in the study and 8851 were recruited and randomly assigned to receive either vitamin D (n=4418) or placebo (n=4433). 8348 participants were included in the fracture and safety analyses (4176 [94·5%] in the vitamin D group and 4172 [94·1%] in the placebo group). Of these, 4125 (49·4%) were female, 4223 (50·6%) were male, and 7701 (92·2%) were of Khalkh ancestry. Median age was 9·2 years (IQR 8·0-10·7) and 7975 (95·5%) participants had baseline serum 25-hydroxyvitamin D concentrations less than 50 nmol/L. During a median follow-up of 3·0 years (IQR 2·9-3·1), 268 (6·4%) participants in the vitamin D group and 253 (6·1%) in the placebo group reported one or more fractures (adjusted RR 1·10, 95% CI 0·93-1·29; p=0·27). Incidence of adverse events did not differ between study groups. INTERPRETATION: Oral vitamin D supplementation at a dose of 14 000 IU/week for 3 years was safe, but did not influence fracture risk in schoolchildren living in Mongolia who had a high baseline prevalence of vitamin D deficiency. FUNDING: US National Institutes of Health.

Tea consumption and risk of bone health: an updated systematic review and meta-analysis.

INTRODUCTION: Current research evaluating the association between tea consumption and bone health still has inconsistent findings. MATERIALS AND METHODS: The electronic databases of Embase, PubMed, Scopus, and Web of Science were systematically searched from inception until December 2022 to identify eligible studies. The calculation of summary relative risks (RRs) and 95% confidence intervals (CIs) was carried out using random-effects models. I2 statistics and Forest plots were used to assess the heterogeneity of RR values across studies. RESULTS: The pooled relative risks for bone health-related outcomes of interest among tea drinkers, compared to non-drinkers, were 0.910 (95% confidence interval 0.845 to 0.980) for fractures, based on 20 studies, 0.332 (0.207-0.457) for BMD (13 studies), 0.800 (0.674-0.950) for osteoporosis (10 studies), and 1.006 (0.876-1.156) for osteopenia (5 studies). Subgroup analysis of locations showed that the pooled relative risks were 0.903 (0.844-0.966) for the hip, 0.735 (0.586-0.922) for the femur, 0.776 (0.610-0.988) for the lumbar, 0.980 (0.942-1.021) for the forearm and wrist, 0.804 (0.567-1.139) for the phalanges, and 0.612 (0.468-0.800) for Ward's triangle. One-stage dose-response analysis revealed that individuals who consumed less than 4.5 cups of tea per day had a lower risk of bone health-related outcomes than those who did not consume tea, with statistically significant results. CONCLUSION: There is an association between tea consumption and a reduced risk of fractures, osteoporosis, hip, femur, and lumbar, as well as increased BMD.

The risk of fractures after entering long-term care facilities.

BACKGROUND: Stratifying residents at increased risk for fractures in long-term care facilities (LTCFs) can potentially improve awareness and facilitate the delivery of targeted interventions to reduce risk. Although several fracture risk assessment tools exist, most are not suitable for individuals entering LTCF. Moreover, existing tools do not examine risk profiles of individuals at key periods in their aged care journey, specifically at entry into LTCFs. PURPOSE: Our objectives were to identify fracture predictors, develop a fracture risk prognostic model for new LTCF residents and compare its performance to the Fracture Risk Assessment in Long term care (FRAiL) model using the Registry of Senior Australians (ROSA) Historical National Cohort, which contains integrated health and aged care information for individuals receiving long term care services. METHODS: Individuals aged ≥65 years old who entered 2079 facilities in three Australian states between 01/01/2009 and 31/12/2016 were examined. Fractures (any) within 365 days of LTCF entry were the outcome of interest. Individual, medication, health care, facility and system-related factors were examined as predictors. A fracture prognostic model was developed using elastic nets penalised regression and Fine-Gray models. Model discrimination was examined using area under the receiver operating characteristics curve (AUC) from the 20 % testing dataset. Model performance was compared to an existing risk model (i.e., FRAiL model). RESULTS: Of the 238,782 individuals studied, 62.3 % (N = 148,838) were women, 49.7 % (N = 118,598) had dementia and the median age was 84 (interquartile range 79-89). Within 365 days of LTCF entry, 7.2 % (N = 17,110) of individuals experienced a fracture. The strongest fracture predictors included: complex health care rating (no vs high care needs, sub-distribution hazard ratio (sHR) = 1.52, 95 % confidence interval (CI) 1.39-1.67), nutrition rating (moderate vs worst, sHR = 1.48, 95%CI 1.38-1.59), prior fractures (sHR ranging from 1.24 to 1.41 depending on fracture site/type), one year history of general practitioner attendances (≥16 attendances vs none, sHR = 1.35, 95%CI 1.18-1.54), use of dopa and dopa derivative antiparkinsonian medications (sHR = 1.28, 95%CI 1.19-1.38), history of osteoporosis (sHR = 1.22, 95%CI 1.16-1.27), dementia (sHR = 1.22, 95%CI 1.17-1.28) and falls (sHR = 1.21, 95%CI 1.17-1.25). The model AUC in the testing cohort was 0.62 (95%CI 0.61-0.63) and performed similar to the FRAiL model (AUC = 0.61, 95%CI 0.60-0.62). CONCLUSIONS: Critical information captured during transition into LTCF can be effectively leveraged to inform fracture risk profiling. New fracture predictors including complex health care needs, recent emergency department encounters, general practitioner and consultant physician attendances, were identified.

Clinical Features, Incidence and Treatment Outcome in Pregnancy-Associated Osteoporosis: A Single-Centre Experience over Two Decades.

Pregnancy-associated osteoporosis (PAO) is a rare syndrome which typically presents with vertebral fractures during pregnancy or lactation. The medical records of sixteen patients with PAO who presented to a specialist clinic at the Western General Hospital in Edinburgh over a 20-year period were reviewed to evaluate the mode of presentation, potential risk factors and response to treatment. The most common presentation was back pain occurring in 13/16 (81.2%) individuals due to multiple vertebral fractures. The diagnosis was usually made postpartum and in 12/16 individuals (75.0%), PAO presented during the woman's first pregnancy. Medicines which could have contributed to the development of PAO included thromboprophylaxis therapies in 8 subjects (50.0%), inhaled or injected corticosteroids in 5 (31.3%), anticonvulsants in 2 (12.5%) and a LHRH agonist in 1 (6.3%). Five individuals reported a family history of osteoporosis, and two pregnancies were complicated by hyperemesis gravidarum. Treatments administered included calcium and vitamin D supplements, bisphosphonates and teriparatide. Bone mineral density increased following the diagnosis in all cases, regardless of treatment given. One patient had further fracture during follow-up, but four patients had subsequent pregnancies without fractures. We estimated that in this locality, the incidence of PAO was 6.8/100,000 pregnancies with a point prevalence of 4.1 per 100,000 women. This case series indicates the importance of family history of osteoporosis and thromboprophylaxis drugs as risk factors for PAO while also demonstrating that the reductions in bone density tend to reverse with time, irrespective of the treatment given.

An epidemiological study of martial arts injuries in patients presenting to US emergency rooms.

INTRODUCTION: With the advent of mixed martial arts (MMA) growing in popularity, there has been a described increase in its participation. The term MMA generally describes the hybridization of combat disciplines including but not limited to: karate, judo, jiu-jitsu, wrestling, taekwondo, boxing, kickboxing, and Muay Thai. With increased participation in MMA and martial arts, differing physical demands are placed on participants. Due to the physical nature of combat sports, there are injuries associated with participation. The purpose of this study is to report the incidence and characteristics of injuries seen from various martial art disciplines presenting to United States Emergency Rooms in order to educate participants and providers alike about risks assumed with participating in martial arts. METHODS: The National Electronic Injury Surveillance System (NEISS) database was queried for martial arts-related injuries from 2009 to 2019. Cases were examined and data including patient age and gender, injury type and location, hospital disposition, and type of martial arts practiced were extracted. RESULTS: A total of 8,400 injuries were recorded, leading to a national estimate of 310,143 martial-arts related injuries over the 11 year period of 2009-2019 (95 % CI 239,063-381,223). The most common types of injuries were strains/sprains (n = 2664, 31.7 %), fractures (n = 1,575, 18.8 %), and contusions/abrasions (n = 1,698, 20.2 %). There were 260 dislocations, with shoulder dislocations being most common (n = 96, 36.9 %). Lower extremities were affected more frequently than upper extremities (n = 3566, 42.5 % versus n = 3026, 36.0 %), with the knee being the single most common location of injury (n = 811, 9.7 %). Males more commonly sustained fractures (19.7 % versus 17.4 %, p = 0.03) and dislocations (3.5 % versus 2.4 %, p = 0.01) when compared to females. Ankle injuries were more common in females than males (10.4 % versus 6.0 %, p < 0.001). Only 2.2 % of patients required admission to the hospital. Risk factors for admission included patients >35 years of age and male sex. CONCLUSION: Martial arts injuries are a significant source of musculoskeletal injuries among patients presenting to US emergency rooms. Lower extremity injuries are seen most frequently, with patients rarely requiring hospital admission. Using this information, both providers and participants may be better equipped to make educated decisions on injury prevention and treatment.

Nonaccidental Pediatric Trauma: Which Traditional Clues Predict Abuse?

OBJECTIVES: The objective of this study is to determine which of the child abuse clues quoted in the literature predict nonaccidental trauma (NAT): history incongruent with injuries found on examination or imaging, old injuries present, history of trauma denied by caregivers, multiple fractures present, changing history, fractures of varied duration, metaphyseal fracture, ear bruise, neck bruise, different history (second historian), and metaphyseal fracture. METHODS: This is a 4-year retrospective study of all suspected NAT cases referred to our medical center. In addition to the index visit, medical records were searched for visits before the index visit with patient historical or physical findings that might have suggested NAT but were not investigated. The association of diagnostic clues and the outcome were assessed by chi-square and logistic regression analysis. RESULTS: For 48 months, there were 109 cases of suspected NAT referred for evaluation (age range, 1 week to 15 years). After formal investigation by an abuse specialist, 79.3% of the cases were considered "likely abuse". Those historical or physical findings with a univariate association with a final conclusion of likely abuse included history incongruent with injuries, old injuries present, trauma history denied, changed history, and retinal hemorrhage. In multivariate logistic regression, only a history incongruent with injures remained an independent predictor of likely abuse (odds ratio, 8.65; 95% confidence interval, 1.74-43.07; P = 0.0151). After review of prior records, in only 2 of 109 cases (1.8%) was there a prior visit where NAT could have been suspected; however, history was thought to be congruent with the injury at the original visits. CONCLUSION: In this 4-year study of NAT, the clinical clue that best predicted likely abuse after expert investigation was a history that was incongruent with the injuries found on emergency department evaluation. The incidence of possible early recognition from a prior emergency department visit in this group was very low, <2% of cases.

Risk of Fractures in Thyroid Cancer Patients With Postoperative Hypoparathyroidism: A Nationwide Cohort Study in Korea.

Postoperative hypoparathyroidism (PO-hypoPT) is an uncommon complication of total thyroidectomy in thyroid cancer patients. Although long-term hypoPT causes characteristic changes in bone metabolism, the risk of fractures in hypoPT remains inconclusive. We investigated the risk of fractures in Korean thyroid cancer patients with PO-hypoPT. This was a retrospective cohort study using data from the Korea Central Cancer Registry and Korean National Health Insurance Service. We analyzed 115,821 thyroid cancer patients aged ≥18 years, who underwent total thyroidectomy between 2008 and 2016. The risk of any fractures, including vertebral, hip, humerus, and wrist fractures, according to parathyroid function after total thyroidectomy, was analyzed using the multivariable Cox proportional hazard model. The PO-hypoPT and preserved parathyroid function groups included 8789 (7.6%) and 107,032 (92.4%) patients, respectively. Over a mean follow-up duration of 4.8 years, 159 (1.8%) and 2390 (2.2%) fractures occurred in the PO-hypoPT and preserved parathyroid function groups, respectively. The risk of any fractures was significantly lower in the PO-hypoPT group than in the preserved parathyroid function group (hazard ratio [HR] = 0.83; 95% confidence interval [CI] 0.70-0.98; p = 0.037) after adjusting for confounders. Regarding the fracture site, only the risk of vertebral fractures was significantly lower in the PO-hypoPT group compared with the preserved parathyroid function group (HR = 0.67; 95% CI 0.47-0.96; p = 0.028) after adjusting for confounders. Subgroup analyses showed that bone mineral density measurements and calcium supplementation interacted with the relationship between PO-hypoPT and the risk of any fractures (p for interactions = 0.010 and 0.017, respectively). PO-hypoPT was associated with a lower risk of fractures in thyroid cancer patients, especially at the vertebra. The relatively low bone turnover caused by PO-hypoPT and appropriate management for PO-hypoPT with active vitamin D and calcium may prevent the deterioration of skeletal health in thyroid cancer patients who can easily be exposed to long-term overtreatment with levothyroxine. © 2023 American Society for Bone and Mineral Research (ASBMR).

Vitamin D supplementation and fracture risk in healthy adults.

Overview of: LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med 2022;387:299-309.

Effectiveness of exercise on fall prevention in community-dwelling older adults: a 2-year randomized controlled study of 914 women.

BACKGROUND: Communal exercise interventions may help prevent falls and injuries. However, pragmatic trials demonstrating the effectiveness of such strategies are sparse. METHODS: We determined whether a cost-free 12-month admission to the city's recreational sports facilities including initial 6 months of supervised weekly gym and Tai Chi sessions decreases the number of falls and related injuries. The mean (SD) follow-up time was 22·6 (4.8) months in 2016-19. A total of 914 women from a population-based sample with a mean age of 76.5 (SD 3.3, range 71.1-84.8) years were randomized into exercise intervention (n = 457) and control (n = 457) groups. Fall information was collected through biweekly short message (SMS) queries and fall diaries. Altogether 1,380 falls were recorded for the intention-to-treat analysis, with 1,281 (92.8%) being verified by telephone. RESULTS: A 14.3% fall rate reduction was detected in the exercise group (Incidence rate ratio (IRR) = 0.86; CI 95% 0.77-0.95) compared with the control group. Approximately half of the falls caused moderate (n = 678, 52.8%) or severe (n = 61, 4.8%) injury. In total, 13.2% (n = 166) of falls (including 73 fractures) required medical consultation with a 38% lower fracture rate in the exercise group (IRR = 0.62; CI 95% 0.39-0.99). Overall, the greatest reduction of 41% (IRR = 0.59; CI 95% 0.36-0.99) was observed in falls with severe injury and pain. CONCLUSIONS: A community-based approach for a 6-month exercise period combined with a 12-month free use of sports premises can reduce falls, fractures and other fall-related injuries in aging women.

Vitamin D: 100 years of discoveries, yet controversy continues.

Over the past 100 years, many major breakthroughs and discoveries have occurred in relation to vitamin D research. These developments include the cure of rickets in 1919, the discovery of vitamin D compounds, advances in vitamin D molecular biology, and improvements in our understanding of endocrine control of vitamin D metabolism. Furthermore, recommended daily allowances for vitamin D have been established and large clinical trials of vitamin D, aimed at clarifying the effect of Vitamin D in the prevention of multiple diseases, have been completed. However, disappointingly, these clinical trials have not fulfilled the expectations many had 10 years ago. In almost every trial, various doses and routes of administration did not show efficacy of vitamin D in preventing fractures, falls, cancer, cardiovascular diseases, type 2 diabetes, asthma, and respiratory infections. Although concerns about side-effects of long-term high-dose treatments, such as hypercalcaemia and nephrocalcinosis, have been around for four decades, some trials from the past 5 years have had new and unexpected adverse events. These adverse events include increased fractures, falls, and hospitalisations in older people (aged >65 years). Several of these clinical trials were powered appropriately for a primary outcome but did not include dose response studies and were underpowered for secondary analyses. Furthermore, more attention should be paid to the safety of high doses of vitamin D supplementation, particularly in older people. In addition, despite universal recommendations by osteoporosis societies for combining calcium supplements with vitamin D there remains insufficient data about their efficacy and effect on fracture risk in the highest risk groups. More trials are needed for people with severe vitamin D deficiency (ie, serum 25-hydroxyvitamin D <25nmol/L [10ng/mL]). In this Personal View, we summarise and discuss some of the major discoveries and controversies in the field of vitamin D.

[Vitamin D supplementation not useful for all older people]. / Vitamine D niet zinvol voor alle 50-plussers.

An estimated 1.5 million Dutch people take vitamin D supplements on prescription, not including those who take multivitamins or vitamin D over the counter. Yet, controversial health benefits of vitamin D supplementation in the general population continues, often explained with not adequately powered studies, combination therapy with calcium, high bolus doses of vitamin D and poor study designs. Recently, the VITAL study does not show an effect in fracture incidence after treatment with daily vitamin D (2000IU) compared to placebo. However, zooming into the results a positive trend is observed in patients with a fragility fracture and/or using anti-osteoporosis medication. Additionally this study does not rule out a positive effect of vitamin D supplementation in severe vitamin D deficiency and high fracture risk patients.

Dietary Inflammatory Index and Fractures in Midlife Women: Study of Women's Health Across the Nation.

CONTEXT: While evidence suggests that chronic, low-grade inflammation is a risk factor for bone loss and fractures, the potential relation between an inflammatory dietary profile and greater fracture risk is uncertain. OBJECTIVE: We examined whether a more inflammatory diet, consumed during pre- and early perimenopause, is associated with more incident fractures starting in the menopause transition (MT) and continuing into postmenopause. METHODS: Dietary inflammatory potential was quantified using 2 energy-adjusted dietary inflammatory index scores: one for diet only (E-DII), and one for diet plus supplements (E-DII-S). We included 1559 women from the Study of Women's Health Across the Nation, with E-DII and E-DII-S scores from the baseline visit (during pre- or early perimenopausal), and up to 20 years of follow-up. We excluded women using bone-beneficial medications at baseline; subsequent initiators were censored at first use. The associations of E-DII or E-DII-S (each tested as separate exposures) with incident fracture were examined using Cox proportional hazards regression. RESULTS: Adjusted for age, BMI, cigarette use, diabetes, MT stage, race/ethnicity, prior fracture, bone-detrimental medication use, aspirin or nonsteroidal anti-inflammatory drug use, and study site, greater E-DII and E-DII-S (tested separately) were associated with more future fractures. Each SD increment in E-DII and E-DII-S predicted 28% (P = .005) and 21% (P = .02) greater fracture hazard, respectively. Associations were essentially unchanged after controlling for bone mineral density. CONCLUSION: A more pro-inflammatory diet in pre- and early perimenopause is a risk factor for incident fracture. Future studies should consider whether reducing dietary inflammation in midlife diminishes fracture risk.

Surgical management of clavicle fractures in Australia: an analysis of Australian Medicare Benefits Schedule database from 2001 to 2020.

BACKGROUND: There is no consensus on the optimal management of clavicle fractures, with advocates of both operative and non-operative management. The objective of this study is to assess the trends in the management of clavicle fractures in Australia over the past two decades. METHODS: The incidence of surgical fixation of clavicle fractures from 2001 to 2020 was analysed using the Australian Medicare Benefits Schedule database, reflective of operations performed on privately insured patients, thus excluding public patients and compensable cases. An offset term was utilized with data from the Australian Bureau of Statistics to account for population changes over the study period. RESULTS: A total of 17 089 procedures for the management of clavicle fractures were performed from 2001 to 2020. The incidence of operative intervention increased from 1.87 per 100 000 in 2001 to a peak of 6.63 per 100 000 in 2016. An overall increase was seen in males (310%) and females (347%) over the study period, as well as across all age groups. A greater proportion of operative interventions was performed on males (n = 14 075, 82%) than females (n = 3014, 18%, P < 0.001). The greatest increase in intervention was noted in those aged 65 or older (14% increase per year, 95% CI 11%-17%, P < 0.05). In 2020, the incidence of operative intervention decreased to a level last seen in 2013. CONCLUSIONS: The incidence of operative interventions for clavicle fractures has increased in Australia over the 20-year study period. This increase is in keeping with recent evidence suggesting several advantages when displaced mid-shaft clavicle fractures are operatively managed.

Characterization of vitamin D deficiency and use of a standardized supplementation protocol in orthopaedic trauma patients.

PURPOSE: The objectives of this study were to assess the incidence of vitamin D deficiency in orthopaedic trauma patients, evaluate the safety and efficacy of a vitamin D supplementation protocol, and investigate the utility of vitamin D supplementation in reducing nonunions. METHODS: Three hundred seventy patients with operative tibia and/or fibula fractures were retrospectively reviewed. Both overall and matched cohorts were analysed. RESULTS: Ninety-eight per cent (n = 210) were found to have vitamin D insufficiency (serum 25(OH)D level < 30 ng/ml). There were no cases of vitamin D toxicity following vitamin D replacement. Median follow-up vitamin D level was 22.7 ng/mL. No statistical difference between union rates was found between either the two consecutive cohorts or matched cohorts. CONCLUSION: This vitamin D replacement protocol was a safe treatment for hypovitaminosis D, but post hoc analysis shows there would need to be over 1200 matched patients to achieve adequate power.