Does Vitamin D affects changes in volumetric bone mineral density and architecture in postmenopausal women after conservatively treated distal radius fractures?

OBJECTIVE: We examined the role of vitamin D on volumetric bone mineral density (vBMD) and architecture during the first week's post-fracture in postmenopausal women (PMW) with distal radial fractures (DRF) treated conservatively using peripheral Quantitative Computed Tomography (pQCT). METHODS: Patients were classified into 2 groups according to initial median 25(OH)D level; Group A (25(OH)D ≥15 ng/ml) and group B (25(OH)D <15 ng/ml). All patients were followed for 12 weeks at three visits: baseline, 6 weeks and 12 weeks post fracture. pQCT was performed at baseline in fractured and contralateral non-fractured radius and at 6th and 12th week on the fractured side. RESULTS: 39 patients completed the protocol. Mean 25(OH)D levels were 15.60±7.35 ng/ml (3.5-41.7). Trabecular (trab) bone mineral content (BMC) and trabvBMD increased at 6 wk. vs. baseline (p<0.001). Cortical BMC, cortvBMD and cross- sectional area (CSA) progressively decreased (p<0.001) during the 12 weeks. There was no interaction between baseline 25(OH)D levels and changes in trabecular and cortical BMC, vBMD and CSA. Advanced age and higher CTX and P1NP were associated with higher cortical bone loss. CONCLUSION: Vitamin D deficiency does not affect the early architectural changes after a DRF. Advanced age and higher bone remodeling were associated with higher cortical bone loss, probably related to immobilization and independent of vitamin D levels.

Elevated Bone Turnover Markers Are Associated With Distal Radius Fractures in Premenopausal Women.

PURPOSE: To examine whether premenopausal women with distal radius fractures (DRF) have lower levels of 25-hydroxyvitamin D (25[OH]D) and increased levels of serum bone turnover markers (BTM) compared with control subjects without fracture. METHODS: Premenopausal women with DRF (n = 20) were prospectively enrolled and compared with age-matched individuals without a fracture (n = 20). Outcome measures included serum levels of 25(OH)D, parathyroid hormone (PTH), markers of bone formation (osteocalcin [OC], N-terminal extension propeptide of type I collagen [P1NP], and bone-specific alkaline phosphatase [BSAP]), and markers of bone resorption (C-terminal telopeptide of type I collagen [CTX]). We assessed associations between BTM and DRF with conditional logistic regression and the utility of markers for fracture prediction with a receiver operator characteristic analysis. RESULTS: The fracture group and control group were comparable in terms of age at menarche and BMI. Patients who had fractures had significantly greater levels of OC and P1NP, and demonstrated a nonsignificant increase in CTX. Levels of 25(OH)D, PTH, and BSAP were similar between groups. Conditional logistic regression revealed independent associations between DRF and increased levels of OC and CTX. Levels of 25(OH)D and PTH were not associated with DRF. Receiver operator characteristic analyses demonstrated moderate performance for OC, P1NP, BSAP, and CTX in predicting DRF. CONCLUSIONS: Levels of 25(OH)D were not associated with DRF in premenopausal women. However, patients with DRF had increased levels of BTM of formation and resorption. Bone turnover markers may be helpful in predicting future fragility fractures in premenopausal women. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Time course of 25(OH)D3 vitamin D3 as well as PTH (parathyroid hormone) during fracture healing of patients with normal and low bone mineral density (BMD).

BACKGROUND: Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OH)D(3) (Vitamin D) as well as PTH (Parathyroid Hormone) the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. METHODS: In the presented study, we analyse the time course of 25(OH)D3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OH)D(3) and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value ≤ 0.05 was considered significant. RESULTS: Serum levels of 25(OH)D(3) showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. CONCLUSIONS: The time course of 25(OH)D(3) and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for therapy and the monitoring of fracture healing.

Evaluation of vitamin D level and grip strength recovery in women with a distal radius fracture.

PURPOSE: Vitamin D is known to contribute to muscular function. The purpose of this study was to determine whether the level of vitamin D is associated with grip strength recovery in women after a distal radius fracture. METHODS: We analyzed grip strength recovery after a distal radius fracture in 70 women over age 50 years. We measured vitamin D levels and grip strength recovery, which we analyzed as a function of age, surgical care, baseline vitamin D level, vitamin D supplementation, wrist range of motion, pain level, and radiographic results at 6 months. We performed multivariate analysis to identify factors that independently predicted grip strength recovery at 6 months after injury. RESULTS: Grip strength of affected hands averaged 65% of the contralateral sides (range, 25% to 100%) at 6 months after injury. We found no significant correlation between baseline vitamin D level and grip strength recovery. However, baseline vitamin D level correlated with the grip strengths of uninjured sides. Multivariate analysis indicated that younger age, vitamin D supplementation, and greater wrist range of motion were independently associated with better grip strength recovery at 6 months after injury. CONCLUSIONS: This study demonstrated that in women with a distal radius fracture, baseline vitamin D level is not associated with grip strength recovery in the injured hand. However, baseline vitamin D level correlated with grip strength in the uninjured hand. In addition, vitamin D supplementation may help grip strength recovery in the injured hand. Further prospective, comparative studies are warranted to confirm the effect of vitamin D supplementation on grip strength recovery.

Calcium homeostasis influences radiological fracture healing in postmenopausal women.

INTRODUCTION: Recent studies suggest that calcium and 25-[OH]-cholecalciferol represent substantial co-factors in fracture healing. However, there still seems to be no sustainable consensus regarding the influence on fracture healing patterns. In this study, the influence of calcium and vitamin D levels on fracture callus formation was prospectively analysed using pQCT scan. METHODS: 94 postmenopausal females with distal radius fractures and consecutive surgery were included. Calcium, 25-[OH]-cholecalciferol, parathyroid hormone and bone-specific alkaline phosphatase levels were obtained prior surgical treatment and after 6 weeks. A pQCT scan was performed on both sites. Bone mineral density and fracture callus area were determined after detecting the outer border contour at a threshold of 280 mg/ccm. Patients received daily supplements of 1000 mg calcium and 880 IU 25-[OH]-cholecalciferol. RESULTS: Mean 25-[OH]-cholecalciferol level was 19.61 ± 21.87 ng/ml, mean parathyroid hormone level was 52.6 ± 58.9 ng/l and mean Ca level was 2.23 ± 0.35 mmol/l. After 6 weeks of supplementation a significant increase of calcium (p < 0.001) and 25-[OH]-cholecalciferol (p < 0.001), and a significant decrease of parathyroid hormone (p < 0.001) levels were observed. Sixth week follow-up fracture callus area correlated significantly with postoperative normal range calcium levels on the fractured site (p = 0.006). Bone mineral density correlated with age (p < 0.001), but not with calcium and 25-[OH]-cholecalciferol levels after 6 weeks. All fractures presented timely adequate callus formation. CONCLUSION: Calcium and parathyroid hormone serum levels influence fracture callus area interpreted as fracture callus formation patterns. Calcium levels within physiological range accounted for highest fracture callus area. Therefore, a balanced calcium homeostasis is required for appropriate callus formation.

25-Hydroxyvitamin-D and Bone Turnover Marker Levels in Patients with Distal Radial Fracture.

BACKGROUND: Fragility fractures are a major public health issue with substantial socioeconomic cost. Vitamin-D deficiency and increased bone turnover are associated with higher rates of bone loss and an increased risk of fracture. We hypothesized that patients with a distal radial fracture would have lower levels of 25-hydroxyvitamin D (25[OH]D) and increased levels of serum bone turnover markers than controls without a fracture. METHODS: Postmenopausal women with a recent distal radial fracture (fracture group, n = 105) were prospectively recruited and were compared with individuals without a fracture (control group, n = 150). Outcome variables included serum levels of 25(OH)D and markers of bone formation, including N-terminal extension propeptide of type-I collagen (P1NP), parathyroid hormone (PTH), bone-specific alkaline phosphatase (BSAP), and osteocalcin, as well as a marker of resorption (C-terminal telopeptide of type-I collagen [CTX-1]). Bone mineral density was measured with dual x-ray absorptiometry. RESULTS: The fracture group was slightly older than the control group (mean and standard deviation [SD], 66.8 ± 10.8 years versus 63.3 ± 9.0 years, p = 0.008), had a lower body mass index (26.4 ± 5.9 kg/m(2) versus 28.0 ± 6.2 kg/m(2), p = 0.05), and more commonly had had a prior fracture (52% versus 31%, p < 0.001). Bone mineral density at the hip was lower in the fracture group than in the control group (0.831 ± 0.130 g/cm(2) versus 0.917 ± 0.139 g/cm(2), p < 0.001). The mean 25(OH)D levels were similar in the fracture and control groups (44.4 ± 14.6 ng/mL versus 41.3 ± 14.5 ng/mL, p = 0.08). Levels of serum markers of bone formation were significantly higher in the fracture group than in the control group (P1NP: 70.4 ± 33.2 ng/mL versus 53.2 ± 25.6 ng/mL, p < 0.001; osteocalcin: 22.3 ± 9.9 ng/mL versus 20.2 ± 9.2 ng/mL, p = 0.017). Levels of BSAP, PTH, and CTX-1 were similar in the two groups. Multivariable logistic regression showed independent associations between a distal radial fracture and low total hip bone mineral density (odds ratio [OR] = 2.02 for each decrease of 1 SD, 95% confidence interval [CI] = 1.38 to 3.01, p < 0.001) and a high P1NP level (OR = 2.17 for each 1-SD increase, 95% CI = 1.52 to 3.06, p < 0.001). CONCLUSIONS: In this cohort, 25(OH)D levels were not associated with distal radial fracture and do not appear to affect the risk assessment for distal radial fracture in postmenopausal women. Patients with a distal radial fracture, however, had increased bone turnover as evidenced by high P1NP and osteocalcin levels. Women with both a high P1NP level and low bone mineral density were at particularly high risk for fracture.

Local effects on the blood gas indices in diaphyseal forearm fractures.

We studied the local changes of blood gas indices of arterialised capillary blood taken simultaneously from the fractured and the uninjured arm of 30 patients with diaphyseal fractures of the forearm. Blood gases were measured with a Stat Profile 5 analyser (Nova Biomedical). The results indicate a slight but statistically significant decrease of the acid-base indices without any changes in the oxygen indices. These slight changes do not affect considerably the diagnosis of the profile.

Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway.

OBJECTIVE: To prospectively study the relation between TSH and risk of hip and forearm fractures. DESIGN: A population-based cohort study. METHODS: In a substudy of the second survey of the Nord Trøndelag Health Study, Norway (HUNT2, 1995-97), linked with a hospital-based fracture registry, we investigated the relation between baseline TSH and risk of hip and/or forearm fractures. POPULATION: A total of 16 610 women and 8595 men aged 40 years or more, without previous self-reported thyroid disease and hip or forearm fractures. RESULTS: During 12.5 years follow-up, a total of 1870 women and 342 men experienced hip or forearm fractures. Overall, there was no relation between baseline TSH and fracture risk. However, there was weak evidence that women with TSH <0.5 and >3.5 mU/l had a slightly increased risk of hip fractures (hazard ratio (HR) 1.30, 95% CI 0.97-1.94 and HR 1.19, 95% CI 0.93-1.52) compared with the reference group with TSH of 1.5-2.4 mU/l. Supplementary analyses showed higher hip fracture risk in women with TSH >4.0 mU/l and negative thyroid peroxidase antibodies (TPOAb) compared with the reference group (HR 1.75, 95% CI 1.24-2.46). CONCLUSION: We found no statistically significant relation between baseline TSH and subsequent fracture risk, but the data suggest a weak positive association with hip fracture risk among women with both low and high TSH. The latter association was confined to women with negative TPOAb status.

Bone mineral density and vitamin D status among African American children with forearm fractures.

OBJECTIVE: To determine whether African American children with forearm fractures have decreased bone mineral density and an increased prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D level ≤ 20 ng/mL) compared with fracture-free control patients. METHODS: This case-control study in African American children, aged 5 to 9 years, included case patients with forearm fracture and control patients without fracture. Evaluation included measurement of bone mineral density and serum 25-hydroxyvitamin D level. Univariable and multivariable analyses were used to test for associations between fracture status and 2 measures of bone health (bone mineral density and 25-hydroxyvitamin D level) while controlling for other potential confounders. RESULTS: The final sample included 76 case and 74 control patients. There were no significant differences between case and control patients in age, gender, parental education level, enrollment season, outdoor play time, height, or mean dietary calcium nutrient density. Cases were more likely than control patients to be overweight (49.3% vs 31.4%, P = .03). Compared with control patients, case patients had lower whole body z scores for bone mineral density (0.62 ± 0.96 vs 0.98 ± 1.09; adjusted odds ratio 0.38 [0.20-0.72]) and were more likely to be vitamin D deficient (47.1% vs 40.8%; adjusted odds ratio 3.46 [1.09-10.94]). CONCLUSIONS: These data support an association of lower bone mineral density and vitamin D deficiency with increased odds of forearm fracture among African American children. Because suboptimal childhood bone health also negatively impacts adult bone health, interventions to increase bone mineral density and correct vitamin D deficiency are indicated in this population to provide short-term and long-term benefits.

Genetic influences on vitamin D status and forearm fracture risk in African American children.

We sought to investigate the relationship between newly identified genetic variants and vitamin D levels and fracture risk in healthy African American (black) children. This case-control study included children of both sexes, ages 5 to 9 years, with and without forearm fractures. Serum 25-hydroxy vitamin D levels, bone mineral density, body mass index, and calcium/vitamin D intake were measured in 130 individuals (n = 60 cases and n = 70 controls). The 5 variants tested were located in the GC gene (rs2282679), in the NADSYN1 gene (rs12785878 and rs3829251), and in the promoter region of the CYP2R1 gene (rs2060793 and rs104741657). Associations between single nucleotide polymorphisms (SNPs) and vitamin D levels were tested using an analysis of covariance. Associations between SNPs and fracture status were tested using logistic regression. The GC gene variant was associated with vitamin D levels (P = 0.038). None of the SNPs were associated with fracture status in young blacks. These results suggest that the variants tested, which are associated with circulating vitamin D levels in whites, are not associated with fracture status in healthy black children. Additional research is required to discover the genetics of fracture risk in blacks.

Vitamin D levels in post-menopausal Korean women with a distal radius fracture.

INTRODUCTION: The purpose of this study was to investigate serum levels of vitamin D in post-menopausal Korean women with a distal radius fracture (DRF) and to determine if there is any association between vitamin D levels and bone-related variables such as bone mineral densities (BMDs), serum parathyroid hormone (PTH) levels and several bone turnover markers. MATERIALS AND METHODS: The data of 104 postmenopausal women surgically treated for a distal radius fracture (DRF group) and 107 age-matched control patients without a fracture (control group) were compared. Serum vitamin D levels (25-hydroxycholecalciferol, 25(OH)D(3)) were compared between the groups with consideration of age and seasonal variations. BMDs, serum PTH and several bone turnover markers, including serum osteocalcin, C-telopeptide and urine N-telopeptide, were measured and analysed to find any association with vitamin D levels. RESULTS: The mean 25(OH)D(3) level was significantly lower in the DRF group compared to the control group (p < 0.001). In particular, patients in their sixth and seventh deciles in the DRF group had significantly lower 25(OH)D(3) levels than patients in the control group (p = 0.001 and 0.013, respectively). When seasonal variation was considered, significant differences of 25(OH)D(3) levels were found between the groups in autumn and winter. Hip BMDs were significantly lower in the DRF group than in the control group, and there was a positive correlation between serum 25(OH)D(3) levels and hip BMDs. Bone turnover markers were not significantly different between the two groups, although serum PTH levels were marginally higher in the DRF group (p = 0.08). CONCLUSIONS: Post-menopausal Korean women with a DRF were found to have significantly lower serum vitamin D levels than the control group, and vitamin D levels were particularly lower in women in their sixth and seventh deciles who may be a good target group for prevention of future fractures. Future investigation should focus on determining whether vitamin D supplementation can be helpful in preventing future fractures in patients with a DRF.

Vitamin D inadequacy is associated with low-energy distal radius fractures: a case-control study.

INTRODUCTION: Vitamin D inadequacy is associated with hip fractures, but the relationship has not been explored for distal radius fractures. AIMS: To compare serum 25-hydroxyvitamin D (s-25(OH)D) status in low-energy distal radius fracture patients and a group of matched controls, and examine whether observed differences in s-25(OH)D between patients and controls would remain after adjusting for bone mineral density (BMD), body mass index (BMI), and smoking history. METHODS: A total of 575 female and 72 male low-energy distal radius fracture patients (50-90 years) and 534 female and 52 male matched controls were included. The primary measure was levels of vitamin D. Secondary measures were BMD assessed by dual energy X-ray absorptiometry, BMI and smoking history. RESULTS: Mean s-25(OH)D was 66.5nmol/L in female patients and 78.7nmol/L in controls (p<0.001). The corresponding figures in men were 64.5 and 77.0nmol/L (p=0.017). In adjusted conditional logistic regression analyzes, s-25(OH)D <50nmol/L (OR=2.32, 95% CI: 1.47-3.64, p<0.001), and 50-75 (OR=1.70, 95% CI: 1.17-2.47, p=0.005) were associated with distal radius fractures in women. s-25(OH)D <50nmol/L (OR=6.27, 95% CI: 1.17-33.66, p=0.032) was associated with distal radius fractures in men. CONCLUSIONS: Vitamin D inadequacy is associated with low-energy distal radius fractures in both women and men. Differences in vitamin D levels are independent of BMD, BMI or smoking history.

Ronacaleret, a calcium-sensing receptor antagonist, has no significant effect on radial fracture healing time: results of a randomized, double-blinded, placebo-controlled Phase II clinical trial.

BACKGROUND: Fractures cause significant morbidity, mortality, and use of health care resources. An oral agent that enhances fracture healing could reduce costs and prevent future disabilities. In Phase I studies, ronacaleret, a novel calcium-sensing receptor antagonist, stimulated parathyroid hormone (PTH) release and increased bone formation markers, suggesting that it may act as an effective oral anabolic agent to enhance fracture healing. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, clinical trial in 85 male and female subjects who had sustained a closed, unilateral, extra-articular fracture of the distal radius and were receiving conservative treatment. Subjects were randomly assigned in a double-blind manner to ronacaleret 200 mg twice daily, ronacaleret 400 mg once daily or matching placebo and followed for 12 weeks. Fracture healing was assessed by radiographs and quantitative computed tomography (CT), and bone turnover markers were measured. The study was terminated early for futility based on the results of an unplanned interim analysis. RESULTS: There were no significant differences between treatment groups in time to radiographic fracture healing (74, 65 and 68 days for placebo, 200 mg twice daily and 400 mg once daily dose groups, respectively), cortical bridging, grip strength, pain and swelling, time to cast removal, or range of motion. Markers of bone formation and levels of whole PTH, intact PTH and serum calcium increased following treatment with ronacaleret. CONCLUSION: Ronacaleret had no significant effect on duration of healing by radiograph or CT scan, time to cast removal, clinical symptoms, grip strength, or range of motion.

Trace metal analysis following locked volar plating for unstable fractures of the distal radius.

An increase in the utilization of metallic devices for orthopaedic interventions from joint replacement to fracture fixation has raised concern over local metal ion release and possible systemic sequelae due to dissemination of these ions. Our purpose was to determine whether serum titanium concentrations were elevated in patients who had previously received a locked volar distal radius plate. Our hypothesis was that the simple presence of titanium alone in a relatively fixed implant was not enough to raise serum titanium levels. Twenty-two potential subjects who had received a volar locked distal radius plate were identified through review of a single surgeon's operative logs. Eleven met inclusion criteria. Serum titanium levels were measured in these subjects and compared to both current and historical control groups. We found no difference between controls and our study group with the exception of one control subject who is employed as a welder. This is in contrast to previous studies from our institution which found increases in titanium levels in hip and spine implants. We conclude that a locking titanium volar distal radius plate does not raise serum titanium levels in this population.

Elevated plasma beta-endorphin/beta-lipotropin concentration following a radius fracture.

Plasma beta-endorphin/beta-lipotropin concentration was assessed soon after a fracture. Blood samples from 14 patients with radius fractures were obtained from both arms soon after admission to the hospital (mean 245 min) after the accident. Follow-up samples were taken after healing of the fractures. Higher plasma beta-endorphin/beta-lipotropin concentrations were found in blood samples taken soon after a fracture in both arms compared with the concentrations after healing of the fracture. At admission, mean beta-endorphin/beta-lipotropin concentrations in the fractured and the contralateral arms were 12.7 pmol/L and 13.2 pmol/L, and after recovery 11.1 pmol/L and 11.5 pmol/L (p = 0.012 and p = 0.041), respectively. The pain decreased according to the visual analogue scale (VAS) (0-10) from 4.64 at admission to 0.58 after healing (p < 0.001). In conclusion, this study showed that beta-endorphin/beta-lipotropin concentrations are increased in both arms following a radius fracture compared to the level after the fracture has healed.