Vitamin D supplementation for children with cancer: A systematic review and consensus recommendations.

BACKGROUND: Prevalent vitamin D deficiency (VDD) and low bone mineral density (BMD) have led to vitamin D supplementation for children with cancer, regardless vitamin D status. However, it remains unsettled whether this enhances bone strength. We sought to address this issue by carrying out a systematic review of the literature. METHODS: We conducted a literature search using PubMed, Embase, and Cochrane databases. Studies including children up to 5 years after cancer therapy were assessed for the association between 25-hydroxyvitamin D (25OHD) levels and BMD Z-scores or fractures, and the effect of vitamin D supplementation on BMD or fractures. Evidence quality was assessed using the GRADE methodology. RESULTS: Nineteen studies (16 observational and 3 interventional, mainly involving children with hematologic malignancies) were included. One study which analyzed 25OHD as a threshold variable (≤10 ng/ml) found a significant association between 25OHD levels and BMD Z-scores, while 25OHD as a continuous variable was not significantly associated with BMD Z-scores in 14 observational studies. We found neither a significant association between lower 25OHD levels and fractures (2 studies), nor between vitamin D (and calcium) supplementation and BMD or fracture frequency (3 studies) (very low quality evidence). CONCLUSION: There is a lack of evidence for an effect of vitamin D (and calcium) supplementation on BMD or fractures in children with cancer. Further research is needed; until then, we recommend dietary vitamin D/calcium intake in keeping with standard national guidelines, and periodic 25OHD monitoring to detect levels <20 ng/ml. Vitamin D/calcium supplementation is recommended in children with low levels, to maintain levels ≥20 ng/ml year-long.

The effect of denosumab in breast cancer patients receiving adjuvant aromatase inhibitors: 36-month results.

INTRODUCTION: Aromatase inhibitor (AI)-associated bone loss increases the risk of bone fracture and reduces patients' quality of life, making it a critical issue worldwide. We conducted a prospective non-randomized clinical trial (UMIN-CTR, UMIN 000016173) to assess the effect of denosumab on bone loss in patients treated with adjuvant AI and have previously reported the results at 12 and 24 months. This study aimed to present the results at 36 months of treatment with denosumab for osteopenia in breast cancer patients who were undergoing treatment with adjuvant AI; 36 months is the longest denosumab treatment period reported so far. MATERIALS AND METHODS: Patients received 60-mg denosumab subcutaneously every 6 months. Daily supplements containing 500-mg elemental calcium and at least 400 international units of vitamin D were highly recommended throughout the study period. The levels of bone mineral density (BMD) and bone turnover markers, serum tartrate-resistant acid phosphatase isoform 5b, and bone alkaline phosphatase were determined at baseline and 6, 12, 18, 24, and 36 months. RESULTS: At 36 months, the bone mineral density of the lumbar spine, right femoral neck, and left femoral neck were found to increase by 8.8% (95% confidence interval CI 7.6-10.1), 4.3% (95% CI 3.0-5.5), and 3.1% (95% CI 2.1-4.1), respectively. No non-traumatic clinical fractures occurred in patients receiving AI and denosumab. CONCLUSION: Twice-yearly administration of denosumab to the breast cancer patients treated with adjuvant AI, regardless of the skeletal site, resulted in consistent increases in BMD without severe adverse events at 36 months.

Fracture risk factors among children living in New Zealand.

Factures are common during childhood. There are limited data available regarding relationships between bone fracture history and calcium intake, sugar sweetened beverages (SSBs) intake, vitamin D status, physical activity (PA), ethnicity, and body composition in New Zealand (NZ) children. Identifying groups of NZ children at risk of fracture and associated predictors may help to improve bone quality during childhood and decrease the risk of fractures throughout life. The aim of this study was to investigate fracture history and associated risk factors in New Zealand children. Children aged 8-12 years were recruited. Capillary blood spots collected from a finger prick were as analyzed for 25(OH)D concentrations. Bioelectrical impedance analysis (InBody720, Seoul, Korea) was used to measure body fat percentage (%BF). Information about fracture history, siblings' history of fractures, family osteoporosis history, PA, ethnicity, and intake of calcium containing foods, and SSBs was collected using questionnaires. Children (n = 647, 354 girls), mean ± SD age 9.8 ± 0.7 years were recruited from six Auckland primary schools. NZ European (n = 252) (NZE) and South Asian (n = 68) children reported the lowest (20.2 %) and highest (44.1 %) fracture incidence, respectively. NZE compared to South Asian children, had higher 25(OH)D concentrations (74.6 ± 19.8 vs. 48.4 ± 19.3 nmol/L, P < 0.001), higher total calcium intake (764.0 ± 394.4 vs. 592.7 ± 266.3 mg/d, P < 0.018), and lower %BF (19.5 ± 6.6 vs. 23.4 ± 8.4, P < 0.003). Maori children had the next highest fracture rate (32.5 %). This group had adequate 25(OH)D (64.2 ± 18.9 nmol/L), but high %BF (23.9 %) and most participated in vigorous PA. After stratifying by sex, binary logistic regression analysis revealed the main determinants of fracture history for boys were high %BF, low 25(OH)D, low calcium intake, high SSBs consumption, siblings' fracture history, family osteoporosis history, and being South Asian; and in girls, high SSBs consumption, siblings' fracture history, and family osteoporosis history. We found South Asian ethnicity was a significant risk factor for boys. Some children were at high risk of vitamin D deficiency and for whom supplementation may be necessary in winter. Good nutrition (especially good sources of calcium and reducing SSBs intakes) should be recommended to children during growth and development to reduce their risk of fractures.

Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis.

Importance: Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness. Objective: To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs. Data Sources: PubMed, EMBASE, Cochrane Library, and other RCT databases were searched from database inception until December 31, 2018. Searches were performed between July 2018 and December 2018. Study Selection: Observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included. Randomized clinical trials compared vitamin D or vitamin D and calcium with control. Data Extraction and Synthesis: Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and assessed possible bias. Rate ratios (RRs) were estimated using fixed-effects meta-analysis. Data extraction and synthesis took place between July 2018 and June 2019. Main Outcomes and Measures: Any fracture and hip fracture. Results: In a meta-analysis of 11 observational studies (39 141 participants, 6278 fractures, 2367 hip fractures), each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted RR for any fracture of 0.93 (95% CI, 0.89-0.96) and an adjusted RR for hip fracture of 0.80 (95% CI, 0.75-0.86). A meta-analysis of 11 RCTs (34 243 participants, 2843 fractures, 740 hip fractures) of vitamin D supplementation alone (daily or intermittent dose of 400-30 000 IU, yielding a median difference in 25[OH]D concentration of 8.4 ng/mL) did not find a reduced risk of any fracture (RR, 1.06; 95% CI, 0.98-1.14) or hip fracture (RR, 1.14; 95% CI, 0.98-1.32), but these trials were constrained by infrequent intermittent dosing, low daily doses of vitamin D, or an inadequate number of participants. In contrast, a meta-analysis of 6 RCTs (49 282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with vitamin D (daily doses of 400-800 IU, yielding a median difference in 25[OH]D concentration of 9.2 ng/mL) and calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (RR, 0.94; 95% CI, 0.89-0.99) and a 16% reduced risk of hip fracture (RR, 0.84; 95% CI, 0.72-0.97). Conclusions and Relevance: In this systematic review and meta-analysis, neither intermittent nor daily dosing with standard doses of vitamin D alone was associated with reduced risk of fracture, but daily supplementation with both vitamin D and calcium was a more promising strategy.

Vitamin D, bone mineral density and risk of fracture in people with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (IDs) have very high rates of osteoporosis and fractures, to which their widespread vitamin D deficiency and other factors could contribute. We aimed to assess in people with IDs previously treated for vitamin D deficiency (1) long-term adherence to vitamin D supplementation and (2) bone mineral density (BMD), as an indicator for risk of fractures, according to vitamin D supplementation and other factors. METHOD: We recorded height, weight, medical, pharmacological, dietary and lifestyle assessment. Blood sample were taken for vitamin D and related analytes. dual-energy X-ray absorptiometry for BMD was performed. RESULTS: Of 51 study participants (mean [standard deviation, SD] age 51.5 [13.6] years, 57% male), 41 (80.4%) were taking vitamin D and 10 were not. Mean [SD] serum vitamin D was 81.3 [21.3] vs. 25.2 [10.2] nmol/L (P < 0.0001), respectively. Thirty-six participants underwent a dual-energy X-ray absorptiometry scan, which showed osteoporosis in 23.7% and osteopenia in 52.6%. Participants on vitamin D had higher BMD than those who were not, a statistically significant difference when confounders (lack of mobility and hypogonadism) were removed. BMD was significantly different according to mobility, particularly in wheelchair users, in whom hip BMD was 33% lower (P < 0.0001) than in participants with normal mobility. Participants still taking vitamin D showed a 6.1% increase in BMD at the spine (P = 0.003) after mean [SD] 7.4 [1.5] years vitamin D treatment. CONCLUSIONS: In people with IDs and previous vitamin D deficiency, BMD increases on long-term vitamin D supplementation. However, additional strategies must be considered for osteoporosis and fracture prevention in this population.

Prevalence of vitamin D deficiency in postmenopausal high- and low-energy fracture patient.

This study evaluated the prevalence of vitamin D deficiency in postmenopausal women with fractures and revealed a high prevalence of vitamin D deficiency regardless of whether the injury mechanism was high or low energy. However, the prescription rate of vitamin D supplementation was lower in the high-energy compared to the low-energy injury group. PURPOSE: The present study aimed to investigate the prevalence of vitamin D deficiency in postmenopausal women with fractures from low-energy and high-energy injuries and to determine differences in the prevalence of vitamin D deficiency and the rate of postoperative vitamin D supplementation between the two groups. METHODS: Medical records of postmenopausal women aged ≥ 50 years who presented with fractures were reviewed. One hundred and thirty-six patients were enrolled and divided into two groups according to the injury mechanism: low (107 patients) vs. high energy (29 patients). Thereafter, serum vitamin D levels, bone turnover markers, body mass index (BMI), bone mineral density, history of prior osteoporosis therapy and vitamin D supplementation, and postoperative prescription rates were compared between the two groups. Vitamin D deficiency was defined as < 20 ng/mL, insufficiency as 20-30 ng/mL, and sufficiency as 30-150 ng/mL. RESULTS: The overall average vitamin D level was 22.6 ng/mL. The prevalence of vitamin D deficiency was 61.8%, and the rate of insufficiency was 14.7%, while only 23.5% of patients showed normal vitamin D levels. The prevalence of vitamin D deficiency was 60.7% and 65.5% in the low and high-energy groups (p = 0.673), respectively. BMI and other laboratory measurements were similar between the two groups. Postoperative calcium and vitamin D supplementation was administered in 85.0% of patients with low-energy injury, as compared to 58.6% of those with high-energy injury (p = 0.003). Osteoporosis medication was also prescribed more frequently in the low-energy group than in the high-energy group (73.8% vs. 48.3%, p = 0.009). In both groups, prescription rates of calcium and vitamin D supplementation and osteoporosis medication increased after the occurrence of fracture. CONCLUSION: Postmenopausal women with fractures have a high prevalence of vitamin D deficiency regardless of whether the mechanism of injury was high or low energy, but the prescription rate of vitamin D supplementation was lower in the high-energy than in the low-energy injury group.

Hypovitaminosis D in Orthopaedic Trauma: Which Guidelines Should Be Followed?

OBJECTIVE: To evaluate the risk factors for hypovitaminosis D and to determine the baseline vitamin D supplementation associated with normal vitamin D levels at presentation. DESIGN: Prospective observational study. SETTING: Level I trauma center. PATIENTS: This study included 259 adult patients undergoing operative treatment for orthopaedic trauma (OTA 11-15, 21-23, 31-34, 41-44, 61-62, 70C, 81-82, 87) between January 1, 2014, and December 31, 2014. INTERVENTION: Prospective, observational study. MAIN OUTCOMES: Association of hypovitaminosis D with patient characteristics, injury factors, and vitamin D supplementation. RESULTS: Univariate predictors of hypovitaminosis D included a lack of preinjury supplementation, non-white race, younger age, female sex, non-Medicare insurance, smoking, obesity, Charlson Comorbidity Index <2, and high-energy mechanism. On multivariate analysis, preinjury supplementation was associated with a lower risk (odds ratio: 0.31, 95% confidence interval: 0.15-0.63, P = 0.001) and non-white race was associated with a higher risk (odds ratio: 3.63, 95% confidence interval: 1.58-8.37, P = 0.001) of hypovitaminosis D. Logistic regression analysis found a dose-dependent relationship between vitamin D supplementation and hypovitaminosis D. Each 100-IU increase in vitamin D supplementation was associated with an 8% decrease in the risk of hypovitaminosis D. CONCLUSIONS: A lack of preinjury supplementation and non-white race were independently associated with hypovitaminosis D. Baseline supplementation consistent with Endocrine Society guidelines (2000 IU daily) was more effective than that consistent with Institute of Medicine guidelines (400 IU daily) in maintaining 25-hydroxyvitamin D above 30 ng/mL in this population. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Treatment of Hypovitaminosis D in an Orthopaedic Trauma Population.

OBJECTIVES: To determine the incidence of hypovitaminosis D and to evaluate a supplementation intervention. We hypothesized that patients would exhibit high adherence with a free sample, and levels would become sufficient. DESIGN: Prospective observational study. SETTING: Level 1 trauma center. PATIENTS: One hundred forty-four consecutive, skeletally mature patients treated for acute fractures. INTERVENTION: All were provided 600 mg calcium and 800 IU vitamin D3 capsules twice daily. MAIN OUTCOME MEASUREMENTS: Serum 25(OH) D levels were obtained on presentation and after supplementation. Patient surveys determined adherence, vitamin D intake, and sun exposure. RESULTS: Ninety-one men and 53 women, mean age 45 years, mean body mass index 28.1, were studied. Mean baseline 25(OH) D level was 20.2 ng/mL, including 9 patients taking vitamin D supplements before injury. All others (mean baseline 16.9 ng/mL) were prescribed calcium and vitamin D and were offered free supplements when discharged. Seventy-seven patients completed surveys, and mean 25(OH) D level was 36.7 ng/mL after a mean of 7.0 weeks of supplementation (P < 0.0001). Seventy-nine percent reported adherence to supplement recommendations. All adherent patients achieved normal levels. Sixteen patients were nonadherent, with 10 who forgot to take the supplement, 4 choosing not to use it, 1 choosing to sell the sample, and 1 losing the sample. CONCLUSION: Hypovitaminosis D was present in 97% of orthopaedic trauma patients who were not already taking supplements. The intervention was effective in reducing hypovitaminosis D within several weeks, with all supplemented patients achieving normal levels. Seventy-nine percent of patients adhered to recommendations. Further study to determine the long-term cost-effectiveness of this strategy seems warranted. LEVEL OF EVIDENCE: Therapeutic, Level II. See Instructions for Authors for a complete description of levels of evidence.

Vitamin D Status and the Relationship with Bone Fragility Fractures in HIV-Infected Patients: A Case Control Study.

HIV-infected patients show high risk of fracture. The aims of our study were to determine the prevalence of vertebral fractures (VFs) and their associations with vitamin D in HIV patients. 100 patients with HIV infection and 100 healthy age- and sex-matched controls were studied. Bone mineral density was measured by quantitative ultrasound at the non-dominant heel. Serum osteocalcin and C-terminal telopeptide of collagen type 1 served as bone turnover markers. Bone ultrasound measurements were significantly lower in patients compared with controls (Stiffness Index (SI): 80.58 ± 19.95% vs. 93.80 ± 7.10%, respectively, p < 0.001). VFs were found in 16 patients and in 2 controls. HIV patients with vertebral fractures showed lower stiffness index (SI) (70.75 ± 10.63 vs. 83.36 ± 16.19, respectively, p = 0.045) and lower vitamin D levels (16.20 ± 5.62 vs. 28.14 ± 11.94, respectively, p < 0.02). The majority of VFs (87.5%) were observed in HIV-infected patients with vitamin D insufficiency, and regression analysis showed that vitamin D insufficiency was significantly associated with vertebral fractures (OR 9.15; 95% CI 0.18-0.52, p < 0.04). VFs and are a frequent occurrence in HIV-infected patients and may be associated with vitamin D insufficiency.

Bone health in long-term gastric cancer survivors: A prospective study of high-dose vitamin D supplementation using an easy administration scheme.

Bone disease in long-term survivors after gastric cancer resection has received little research attention. This study aimed to investigate bone health after curative resection of gastric cancer and the consequences of high-dose vitamin D supplementation in patients with low levels of 25-(OH)-vitamin D. Disease-free patients at least 24 months after gastric cancer resection represented the study cohort. Serum markers of bone metabolism were assessed at baseline and at 3 and 12 months. Bone mineral density and presence of fractures were assessed by X-ray at baseline. Patients with 25-(OH)-vitamin D ≤30 ng/mL at baseline received 16,000 IU of vitamin D3 every 10 days during the 1-year follow-up. Forty patients were included in the study. Mean time from surgery was 48.9 (24-109) months. Vitamin D insufficiency and secondary hyperparathyroidism were observed in 38 and 20 patients, respectively. Densitometry showed osteoporosis in 14 women and seven men and prevalent fractures in 12 women and six men at baseline. After 3 months of vitamin D supplementation, 35 patients reached values of 25-(OH)-vitamin D over 30 ng/mL. After 12 months, 38 patients were in the normal range of 25-(OH)-vitamin D. At the same time, iPTH levels and markers of bone turnover (C-terminal cross-linked telopeptide of type-I collagen, serum concentrations of bone-specific alkaline phosphatase and osteocalcin) significantly decreased after vitamin D intervention. Oral administration of high doses of vitamin D is easily implemented and restored 25-(OH)-vitamin D and iPTH values, which are frequently disturbed after gastric cancer resection.

Effect of Combination Folic Acid, Vitamin B6 , and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial.

Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12 , B6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard = 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. © 2017 American Society for Bone and Mineral Research.

Effect of Vitamin D on Falls and Physical Performance.

Recent understanding has highlighted the importance of extraskeletal role of vitamin D. Despite numerous observational and interventional studies over the last two decades, the apparent divergent clinical findings have intensified the controversy regarding this role of vitamin D in older adults. This article reviews the existing literature and summarizes the current knowledge of vitamin D status and vitamin D supplementation on falls and physical performance, describes the putative mechanisms underlying this association, and reflects on the controversy surrounding vitamin D recommendations in older adults.

Vitamin D Effect on Bone Mineral Density and Fractures.

One hundred years ago, vitamin D was identified as the cause and cure of osteomalacia. This role remains firmly established. Vitamin D influences skeletal mineralization principally through the regulation of intestinal calcium absorption. It has been proposed that vitamin D has direct beneficial effects on bone (besides the prevention of osteomalacia), but these have been difficult to establish in clinical trials. Meta-analyses of vitamin D trials show no effects on bone density or fracture risk when the baseline 25-hydroxyvitamin D is >40 nmol/L. A daily dose of 400 to 800 IU vitamin D3 is usually adequate to correct such deficiency.

Fractures in patients with CKD-diagnosis, treatment, and prevention: a review by members of the European Calcified Tissue Society and the European Renal Association of Nephrology Dialysis and Transplantation.

Mineral and bone disease is omnipresent in patients with chronic kidney disease (CKD) and leads to a diverse range of clinical manifestations, including bone pain and fractures. The accumulation of traditional clinical risk factors, in addition to those related to CKD, enhances the risk of comorbidity and mortality. Despite significant advances in understanding bone disease in CKD, most clinical and biochemical targets used in clinical practice remain controversial, resulting in an undermanagement of bone fragility. Vitamin D supplementation is widely used, but only a few studies have shown beneficial effects and a reduced risk of fracture and mortality. The achievement of serum levels of 25-hydroxyvitamin D is recommended for CKD patients to reduce a high parathyroid hormone level, which is associated with skeletal fractures. Optimal control of parathyroid hormone also improves bone mineralization and lowers circulating bone biomarkers such as alkaline phosphatase and cross-linked collagen type I peptide. The potential value of more recent biomarkers such as sclerostin and fibroblast growth factor 23, as surrogates for bone fragility, is an encouraging new direction in clinical research but is far from being firmly established. This article reviews the literature related to the pathophysiological role of various mineral and biochemical factors involved in renal osteodystrophy. To better understand bone fragility in CKD, new information related to the impact of disturbances of mineral metabolism on bone strength is urgently needed. The combined expertise of clinicians from various medical disciplines appears crucial for the most successful prevention of fractures in these patients.

Change in serum level of vitamin D and associated factors at early phase of bone healing among fractured adult patients at University of Gondar teaching hospital, Northwest Ethiopia: a prospective follow up study.

INTRODUCTION: Currently, Vitamin D deficiency is a major public health problem and it affects more than one billion people worldwide. Vitamin D is crucial for bone mineralization and ossification. Patients with fractures need Vitamin D for the healing of their fractured bone. The current study was carried out to determine if there is change in the serum level of Vitamin-D associated with factors at early phase of fractured bone healing (ossification) process among adult fractured patients at University of Gondar teaching hospital, Northwest Ethiopia. METHODS: This facility-based prospective follow up study was conducted from March to June 2016. Data was collected by an interviewer, and pretested and structured questionnaires were used. Biological samples were collected to determine the serum level of vitamin-D in all subjects. In addition, X-Ray findings were used to determine the early phase of bone healing process. Data was entered into EPI INFO version 3.5.3 and analyzed using the Statistical Package for Social Sciences (SPSS) version 20. Both bivariate and multivariate logistic regression analysis was done to screen for factors associated with decreased serum levels of Vitamin-D. In the Multivariate regression analysis, those variables which had a P-value of <0.05 were considered as independently associated with change in serum level of Vitamin-D. RESULTS: A total of 118 adult patients with fractures participated in this study. The prevalence of patients' with decreased serum levels of vitamin-D at post-test was 63.6% [95% CI; (0.551-0.720)]. Inadequate intake of milk and milk products in the 1st week of fracture [AOR = 95%CI: 0.20 (0.05-0.90)], Poor Dietary Diversity Score [AOR = 95% CI: 29.1 (2.27-371.65)], and ossified bone [AOR =95% CI: 4.10 (1.12-14.95)] showed statistically significant association with decreased serum level of Vitamin-D. CONCLUSION AND RECOMMENDATIONS: Decreased serum level of Vitamin-D at early phase of fractured bone healing process was found in the majority of patients (>63%) raising concern for Vitamin D deficiency to be a significant public health problem in the study population. It was statistically associated with: poor dietary diversity score, in adequate intake of milk and milk products in the 1stone week of fracture and ossified (healed) bone. Introducing hospital based Vitamin-D supplementation and integrated with health and nutritional education is a vital intervention needed to improve serum levels of Vitamin-D.

Evaluation of bone turnover markers and serum minerals variations for predicting fracture healing versus non-union processes in adult sheep as a model for orthopedic research.

Bone turnover markers (BTMs) have been considered as an auxiliary method of following the fracture healing process and for early prediction of impaired bone healing. A better understanding of the potential of BTMs in this application could allow for earlier interventions and improved patient care. The aim of this study with a large animal experimental model was to assess the variation of bone formation markers - namely the total alkaline phosphatase (ALP) and its bone-specific isoform (BALP), serum concentration of intact osteocalcin (OC), N-terminal propeptide type III procollagen (PIIINP) and of bone resorption markers - namely tartrate resistant acid phosphatase (TRAP) and deoxypyridinoline crosslink (DPD) during the first stages of a normal fracture healing process and of a segmental critical size defect (CSD), which progresses to a non-union process. Thirty healthy female sheep (Portuguese Churra-da-Terra-Quente breed), approximately 4-years-old, were enrolled in this study. Jugular venous blood samples were collected pre-operatively and at 1, 2, 3, 4, 6, 8, 10 and 12 post-operative weeks. The animals of the CSD group showed significant lower serum levels of BALP, OC and significant higher serum PIIINP levels at early stages of the fracture healing process, compared with animals that progressed in a normal fracture healing process. Serum BALP, OC and PIIINP levels could be useful as non-invasive auxiliary tools with other complementary methods for predicting the outcome of traumatic bone fractures.

Bone fracture in severe small-for-gestational-age, extremely low birth weight infants: A single-center analysis.

INTRODUCTION: Bone fracture is a complication of extremely low birth weight infants (ELBWIs). This study aimed to analyze risk factors for bone fracture in a population of severe small-for-gestational-age (SGA) ELBWIs. METHODS: We retrospectively studied data from ELBWIs with a birth weight <1000g and <-2 standard deviations (SDs) born at the National Center for Child Health and Development, Japan, from 2013 to 2015. Infants were divided into fracture and control groups. Serum calcium (Ca) and phosphorus (P) levels, perinatal factors, and previously reported risk factors were analyzed. RESULTS: Of 25 cases of severe SGA ELBWIs, 5 cases of bone fracture were identified. Gestational age was 27.7±2.2, 29.1±2.6weeks (mean difference [MD] -1.4, 95% confidence interval [CI]: -4.0, -1.2, p=0.280), birth weight (BW) 448±105, 673±216g (MD -225, 95% CI: -433, -17, p=0.036) and BW-SD -4.1±0.1, -3.4±0.8 (MD -0.8, 95% CI: -1.5, -0.02, p=0.045) in the fracture and control groups, respectively. Minimums of serum Ca and P were 6.6±1.4, 8.1±0.8mg/dl (MD -1.5, 95% CI: -2.5, -0.6), p=0.003) and 2.3±0.6, 3.5±1.1mg/dl (MD -1.2, 95% CI: -2.2, -0.1, p=0.027) in the fracture and control groups, respectively. CONCLUSION: Lower BW and BW-SD were possible risk factors for bone fracture. Hypocalcemia and hypophosphatemia may also contribute to the condition.

Do 25-Hydroxyvitamin D Levels Correlate With Fracture Complications?

OBJECTIVES: To determine the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and the likelihood of postoperative complications and fracture reoperation rate in orthopaedic trauma patients receiving vitamin D and calcium supplementation. DESIGN: Retrospective case series. SETTING: Level I trauma center, Midwestern United States. PATIENTS: All orthopaedic trauma patients-18 years or older-over a 20-month period were included with available initial and repeat 25(OH)D serum levels. In total, 201 patients met inclusion criteria. INTERVENTION: All patients received 1000 IU of vitamin D3 and 1500 mg of calcium daily. Vitamin D deficient and insufficient patients also received 50,000 IU of ergocalciferol (vitamin D2) weekly until 25(OH)D levels normalized or fractures healed. MAIN OUTCOME MEASUREMENTS: fracture complications and 25(OH)D levels. RESULTS: Fifteen patients experienced postoperative healing complications. There was no significant difference between initial (P = 0.92) or repeat (P = 0.91) 25(OH)D levels between patients with and without fracture healing complications. Twenty-eight patients required repeat orthopaedic surgery. There was no significant difference between initial (P = 0.62) or repeat (P = 0.18) 25(OH)D levels between patients who did or did not require repeat orthopaedic surgery. There was no significant difference between initial (P = 0.66) or repeat (P = 0.89) 25(OH)D levels between patients who did or did not require nonorthopaedic surgery. CONCLUSIONS: Serum 25(OH)D levels did not significantly affect the likelihood of fracture healing complications requiring surgery or any nonorthopaedic injury-related surgery. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Conventional and New Antiepileptic Drugs on Vitamin D and Bone Health: What We Know to Date?

The treatment with antiepileptic drugs (AEDs), in particular conventional drugs, induces an increased risk of fractures in women and in epileptic patients in treatment with AEDs for more than 12 years. A supplementation with calcium and vitamin D is suggested in patients chronically treated with some AEDs and there are recommendations to do so. The lack of significant conclusive evidence about the effects of conventional and newer AEDs on bone metabolism needs for more clinical studies in order to perform an appropriate use of calcium and vitamin D supplementation in young and ederly epileptic patients.