Preoperative Thyroid-Stimulating Hormone Levels and Three-Year Mortality in Elderly Hip Fracture Patients: Insights from a Prospective Cohort Study.

BACKGROUND It is unclear whether preoperative thyroid-stimulating hormone (TSH) level is correlated with long-term mortality in the elderly after hip fracture surgery. We aimed to assess the association between TSH levels and 3-year mortality in these patients. MATERIAL AND METHODS We enrolled patients aged 65 and above who had hip fracture surgery and thyroid function tests upon admission from 2018 to 2019. Patients were categorized based on TSH median value, quartiles, or thyroid function status. The median follow-up time was 3.1 years. Cox proportional hazards models were used to examine the correlation between TSH levels and mortality, adjusting for covariates. RESULTS Out of 799 eligible patients, 92.7% (741/799) completed the follow-up, with 20.6% (153/741) of those having died by the end of the follow-up. No statistically significant differences in mortality risks were found when stratified by TSH median value (HR 0.88, 95% CI 0.64-1.22, P=0.448) or quartiles (HR ranging from 0.90 to 1.13, P>0.05). Similarly, when categorized based on admission thyroid function status, patients who presented with hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism upon admission did not demonstrate a statistically significant difference in mortality risk compared to those who were considered euthyroid (HR 1.34, 95% CI 0.72-2.49, P=0.359; HR 0.77, 95% CI 0.38-1.60, P=0.489; HR 1.15, 95% CI 0.16-8.30, P=0.890; HR 1.07, 95% CI 0.34-3.38, P=0.913, respectively). CONCLUSIONS Admission TSH is not significantly associated with 3-year mortality in geriatric patients after hip fracture surgery.

Association between preoperative persistent hyperglycemia and postoperative delirium in geriatric hip fracture patients.

BACKGROUND: The management of preoperative blood glucose levels in reducing the incidence of postoperative delirium (POD) remains controversial. This study aims to investigate the impact of preoperative persistent hyperglycemia on POD in geriatric patients with hip fractures. METHODS: This retrospective cohort study analyzed medical records of patients who underwent hip fracture surgery at a tertiary medical institution between January 2013 and November 2023. Patients were categorized based on preoperative hyperglycemia (hyperglycemia defined as ≥ 6.1mmol/L), clinical classification of hyperglycemia, and percentile thresholds. Multivariate logistic regression and propensity score matching analysis (PSM) were employed to assess the association between different levels of preoperative glucose and POD. Subgroup analysis was conducted to explore potential interactions. RESULTS: A total of 1440 patients were included in this study, with an incidence rate of POD at 19.1% (275/1440). Utilizing multiple logistic analysis, we found that patients with hyperglycemia had a 1.65-fold increased risk of experiencing POD compared to those with normal preoperative glucose levels (95% CI: 1.17-2.32). Moreover, a significant upward trend was discerned in both the strength of association and the predicted probability of POD with higher preoperative glucose levels. PSM did not alter this trend, even after meticulous adjustments for potential confounding factors. Additionally, when treating preoperative glucose levels as a continuous variable, we observed a 6% increase in the risk of POD (95% CI: 1-12%) with each 1mmol/L elevation in preoperative glucose levels. CONCLUSIONS: There exists a clear linear dose-response relationship between preoperative blood glucose levels and the risk of POD. Higher preoperative hyperglycemia was associated with a greater risk of POD. CLINICAL TRIAL NUMBER: NCT06473324.

Predictive value of the early postoperative hemoglobin-to-red blood cell distribution width ratio for acute kidney injury in elderly intertrochanteric fracture patients.

BACKGROUND: Hemoglobin-to-red blood cell distribution width ratio (HRR) had great predictive value for the prognosis of malignant tumors and cardiovascular disease. However, its predictive value for the occurrence of acute kidney injury (AKI) in elderly intertrochanteric fracture patients remains unclear. This study aims to analyze the correlation between the early postoperative HRR and the risk of postoperative AKI in elderly intertrochanteric fracture patients. METHODS: We reviewed the medical records of 307 elderly intertrochanteric fracture patients in this single-center retrospective cohort study. We performed univariate analysis on the relevant parameters, and parameters with significant differences were included in the following logistic regression model for multivariate analysis. Then, we used a receiver operating characteristic (ROC) curve to evaluate the predictive value of the early postoperative HRR level for AKI in elderly intertrochanteric fracture patients. Patients were divided into a high HRR group and a low HRR group according to the cutoff point determined by ROC curve analysis. Subsequently, the relevance between postoperative HRR and AKI was further determined using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: The area under the curve of the early postoperative HRR for predicting postoperative AKI was 0.714 (95% CI: 0.618-0.809). The cutoff value was 5.44. The sensitivity was 72.7%, and the specificity was 70.8%. Patients were divided into low HRR (⩽ 5.44) and high HRR (> 5.44) groups according to the cutoff value. PSM and IPTW analysis indicated that the risk of AKI in the low HRR group was significantly higher than that in the high HRR group in both the matched cohort (OR = 6.914, 95% CI: 1.714-46.603, p = 0.016) and the weighted group (OR = 2.784, 95% CI: 1.415-5.811, p = 0.040). CONCLUSIONS: Early postoperative HRR is an accurate, accessible, and economical blood test parameter that can predict the risk of postoperative AKI in elderly patients with femoral intertrochanteric fracture.

Serum levels of irisin in postmenopausal women with osteoporotic hip fractures.

OBJECTIVE: The purpose of this study was to evaluate the role of circulating serum levels of irisin in predicting hip fracture occurrence in a cohort of Chinese postmenopausal women. METHODS: This was a cross-section and case-control study. Four hundred and thirty postmenopausal women aged 50-90 years were included (215 with hip fractures and 215 age-matched cases without fracture). Clinical features, bone mineral density (BMD) and serum biomarkers levels including irisin were measured at baseline. Cox proportional hazards regression analysis was used to assess the correlation between irisin and fracture risk. RESULTS: The mean age of those participants was 68.7 (S.D. 11.7) and 53.0% were order than 65. The irisin serum levels were positively related to total body BMD and total hip BMD. Women with hip fractures showed lower mean serum levels of irisin compared normal control women (457.6 ± 172.6 ng/ml vs. 602.2 ng/ml; P < 0.001). The irisin levels in third and fourth quartiles were associated with the risk of hip fracture (the lowest quartile of irisin levels as the reference), and risk of fracture reduced by 67% (hazard ratio [HR] = 0.33; 95 %CI: 0.18-0.54; P < 0.001) and 84% (HR = 0.16; 95 %CI: 0.09-0.29; P < 0.001). The irisin levels in third and fourth quartiles were also associated with the risk of osteoporosis, and risk of fracture reduced by 55% (HR = 0.45; 95 %CI: 0.21-0.63; P = 0.003) and 73% (HR = 0.27; 95 %CI: 0.15-0.47; P < 0.001). CONCLUSION: Decreased serum levels of circulating irisin are associated with high risk of osteoporosis-related hip fractures and osteoporosis.

Changes of bone turnover markers after elderly hip fracture surgery.

INTRODUCTION: Bone turnover markers (BTMs) can be used to monitor bone metabolism, while the actual clinical changing in hip fracture had not been certified to evaluate the changes of BTMs during the healing process after surgery of elderly hip fractures; and to get the effects of operation type, gender, serum 25(OH)D level, and age on bone turnover markers. MATERIALS AND METHODS: A total of 100 elderly cases with hip fracture were selected, including 74 females and 26 males, and the patients were followed to 180-230 days after surgery. Serum levels of N-propeptide of type 1 collagen (P1NP), C-terminal crosslinking telopeptides of type 1 collagen (CTX), Osteocalcin (OC), and 25 hydroxy vitamin D (25OHD) were investigated. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry (DXA). RESULTS: (1) P1NP and CTX showed peak time at 30-60 days after operation, while OC keep going even at 180-230 days; P1NP showed less than 4 times elevation during healing, CTX and OC only had less than 2 times rise. (2) Female had higher serum CTX and OC than male, intramedullary nailing for intertrochanteric fracture patients had higher P1NP than hip replacement for femoral neck fracture patients, and both the degrees of increase were less than 50%. (3) Serum average 25(OH)D level had no effect on BTMs during the fracture healing; different from the young old (65-84 years), serum OC level of eldest older patients(≥ 85 years) decreased early in the process of fracture healing. CONCLUSIONS: BTMs reached the peak level in 30-60 days after surgery, P1NP showed less than 4 times elevation, and CTX and OC had less than 2 times rise. It was not necessary to take gender into account when observing P1NP, and it was not necessary to take fracture and operation type into account when observing CTX and OC.

Decrease in serum calcitriol (but not free 25-hydroxyvitamin D) concentration in hip fracture healing.

OBJECTIVE: To assess the decrease in serum calcitriol concentrations after hip fracture. METHODS: Serum concentrations of calcitriol, 25(OH)D, parathyroid hormone (PTH), directly measured free 25(OH)D, and indices of bone formation were measured in elderly patients with hip fracture (HF) and patients with elective hip replacement (EHR) at admission and after 7 weeks. RESULTS: A total of 45 patients with HF and 17 patients with EHR completed this prospective study. Baseline serum calcitriol levels were ≤ 60 pmol/l in 26% of the HF patients. After 7 weeks, they significantly decreased (p < 0.001). In patients with EHR, serum calcitriol was within the reference range in all but one patient and did not change during the 7-week recovery phase. Seven weeks after HF, a significant positive relationship was observed between the change in calcitriol and serum 25(OH)D concentration (r = 0.385, p = 0.009) and free 25(OH)D (r = 0.296, p = 0.048), and a decrease in calcitriol during recovery was associated with a decrease in serum PTH (p = 0.038). Seven weeks after HF, changes in both serum PTH and serum 25(OH)D concentrations contributed to the prediction of changes in serum calcitriol (R2 = 0.190, p = 0.012). CONCLUSIONS: Unlike patients with EHR, subjects with HF had low serum 25(OH)D and low free 25(OH)D concentrations at admission, while their serum 1,25D levels were relatively elevated. Decreases in circulating calcitriol levels in the 7 weeks following hip surgery were associated with a resolution of secondary hyperparathyroidism and low availability of free 25(OH)D.

Sub-optimal serum 25-hydroxyvitamin D level affects 2-year survival after hip fracture surgery.

INTRODUCTION: Hypovitaminosis D is a common condition seen in patients with acute hip fracture. We hypothesize that in addition to the other prognosticating factors, hypovitaminosis D may affect survival in patients treated for hip fractures. The objective of this study is to evaluate the impact of serum level of 25-hydroxyvitamin D (25(OH)D) on the survivability after surgical fixation of hip fractures. MATERIALS AND METHODS: We retrospectively studied data collected from January 2013 through December 2015 at a large tertiary hospital in Singapore. Patient's age, gender, Charlson Comorbidity Index (CCI), delay of surgery, fracture patterns, ASA score, as well as their pre-operative serum levels of 25(OH)D, albumin and calcium were examined. Univariate and multivariate logistic regression were used to analyse post-operative outcomes including short (inpatient, 30 and 90 days) and long-term mortality (2 years). RESULTS: Data from 1004 patients were used. Information on the serum level of 25(OH)D was available in 80% of them (n = 801) and more than 90% (n = 735) of the patients had a baseline serum level of less than 30 ng/ml. Mortality rate within this group were 1.1% (n = 9) at 30 days, 1.9% (n = 15) at 90 days and 11.0% (n = 88) at 2 years follow up. Hypovitaminosis D was not a significant risk predictor for short-term mortality, but found to be a significant predictor at 2 years. CONCLUSIONS: In this study, we showed a high prevalence of hypovitaminosis D among the osteoporotic hip fracture population and its impact on 2-year survivorship after hip fracture surgery.

Circulating Myostatin Levels Decrease Transiently after Implantation of a Hip Hemi-Arthroplasty.

INTRODUCTION: Muscle and bone metabolism are both important for the healing of fractures and the regeneration of injured muscle tissue. The aim of this investigation was to evaluate myostatin and other regulating factors in patients with hip fractures who underwent hemi-arthroplasty. METHODS: Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf-1 (Dkk1), and periostin (PSTN) as well as markers of bone turnover were evaluated in patients with hip fractures before surgery and twice in the 2 weeks after surgery. These parameters were also evaluated in age- and gender-matched subjects without major musculoskeletal injury. RESULTS: MSTN was transiently reduced; its opponent FSTN was transiently increased. Dkk1, the negative regulator of bone mass, and PSTN, a marker of subperiosteal bone formation, increased after surgery. With regard to markers of bone turnover, resorption was elevated during the entire period of observation whereas the early bone formation marker N-terminal propeptide of type I collagen was elevated 12 days after surgery. CONCLUSIONS: Unexpectedly, MSTN, a negative regulator of muscle growth, was reduced after surgery compared with before surgery. As musculoskeletal markers are altered during bone healing, they do not reflect general bone metabolism after fracture or joint arthroplasty. This is important because many elderly patients receive treatment for osteoporosis.

Novel biomarkers for prediction of outcome in hip fracture patients-An exploratory study.

BACKGROUND: Little is known about the value of biomarkers for prognostication in hip fracture patients. The main objective of the present study was to assess if biomarkers add useful information to an existing risk score for prediction of 30-day mortality in patients suffering from out of hospital hip fractures. METHODS: In a prospective observational single centre study, association between plasma concentration of ninety-two biomarkers at admission and 30-day mortality was analysed using logistic regression adjusted for risk factors included in Nottingham Hip Fracture Score (NHFS). Biomarkers associated with the outcome in the adjusted analysis were further evaluated by calculating the net reclassification improvement (NRI) and the change in area under the receiver operating characteristics curve (AUC) relative to the NHFS. RESULTS: 997 patients were included. Sixty-two patients died within 30 days (6.2%). Eleven biomarkers were associated with 30-day mortality in adjusted analysis. Of these biomarkers Growth Differentiation Factor-15 (GDF-15) had NRI for the primary outcome (12.1%; 95% CI: 1.2-23.3) and Carbohydrate Antigen 125 (CA-125) improved the AUC relative to NHFS (improvement: 0.05; 95% CI: 0.01-0.10, P = .027). Both CA-125 and GDF-15 improved the AUC for a composite outcome of 30-day mortality and cardiovascular complications. CONCLUSIONS: Adding GDF-15 or CA-125 to the Nottingham Hip Fracture Score improves the discrimination with regard to predicting 30-day mortality and may help to identify a subgroup of hip fracture patients with a particularly poor prognosis. The value of these biomarkers should be explored in further studies to confirm clinical utility.

The increase of osteopontin and ß-carboxy-terminal cross-linking telopeptide of type I collagen enhances the risk of hip fracture in the elderly.

BACKGROUND: Hip fracture in the elderly is a health burden worldwide due to its high mortality rate. This study was conducted to determine the possible mechanisms of osteopontin (OPN) and ß-carboxy-terminal cross-linking telopeptide of type I collagen (ß-CTX) in hip fracture in the elderly. MATERIALS AND METHODS: In the study, we recruited 108 elderly patients with hip fracture diagnosed from May 2012 to May 2015 at the Third Hospital of Xiamen and 86 healthy individuals without a history of hip fracture were taken as controls. Serum levels of OPN and ß-CTX were then determined. The T and Z values for bone mineral density (BMD) were also measured. Moreover, logistic regression analysis was performed to assess the risk and protective factors for hip fracture in the elderly. RESULTS: Serum levels of both OPN and ß-CTX were increased in elderly patients with hip fracture. OPN was positively correlated with ß-CTX. In addition, the levels of OPN and ß-CTX shared a positive association with the age, and a negative association with the BMD, in terms of T and Z values of the hip. In addition, increased BMD and outdoor sports might be protective factors for hip fracture, and an increase in levels of OPN and ß-CTX might be associated with a higher risk of hip fracture in the elderly population. DISCUSSION: Collectively, increased serum levels of OPN and ß-CTX might be correlated with a higher risk of a hip fracture and have predictive values in the occurrence of hip fracture in the elderly.

The necessity of routine postoperative laboratory tests after total hip arthroplasty for hip fracture in a semi-urgent clinical setting.

BACKGROUND: Recent studies suggest that routine postoperative laboratory tests are not necessary after primary elective total hip arthroplasty (THA). This study aims to evaluate the utility of routine postoperative laboratory tests in patients undergoing THA for hip fracture in a semi-urgent clinical setting. MATERIALS AND METHODS: This retrospective study included 213 consecutive patients who underwent primary unilateral THA for hip fractures. Patient demographics, clinical information, and laboratory tests were obtained from the electronic medical record system. Multivariate logistic regression analysis was performed to identify risk factors associated with abnormal laboratory test-related interventions. RESULTS: A total of 207 patients (97.18%) had abnormal postoperative laboratory results, which were mainly due to anemia (190/213, 89.20%) and hypoalbuminemia (154/213, 72.30%). Overall, 54 patients (25.35%) underwent a clinical intervention, 18 patients received blood transfusion, and 42 patients received albumin supplementation. Factors associated with blood transfusion were long operative time and low preoperative hemoglobin levels. Factors associated with albumin supplementation were long operative time and low preoperative albumin levels. Of the 33 patients with abnormal postoperative creatinine levels, 7 patients underwent a clinical intervention. For electrolyte abnormalities, sodium supplementation was not given for hyponatremia, three patients received potassium supplementation, and one patient received calcium supplementation. CONCLUSIONS: This study demonstrated a high incidence of abnormal postoperative laboratory tests and a significant clinical intervention rate in patients who underwent THA for hip fracture in a semi-urgent clinical setting, which indicates that routine laboratory tests after THA for hip fracture are still necessary for patients with certain risk factors. LEVEL OF EVIDENCE: Level III. Trial registration Clinical trial registry number ChiCTR1900020690.

Biochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study.

The relationships of osteocalcin (OC) and C-telopeptide of type I collagen (CTX) with long-term incidence of hip fracture were examined in 1680 post-menopausal women from a population-based study. CTX, but not OC, levels were associated with incident hip fracture in these participants, a relationship characterized by an inverted U-shape. INTRODUCTION: We sought to investigate the relationships of OC, a marker of bone formation, and CTX, a marker of bone resorption, with long-term incidence of hip fracture in older women. METHODS: We included 1680 women from the population-based Cardiovascular Health Study (mean [SD] age 74.5 [5.0] years). The longitudinal association of both markers with incidence of hip fracture was examined using multivariable Cox models. RESULTS: During a median follow-up of 12.3 years, 288 incident hip fractures occurred. Linear spline analysis did not demonstrate an association between OC levels and incident hip fracture. By contrast, increasing levels of CTX up to the middle-upper range were associated with a significantly greater risk of hip fracture (HR = 1.52 per SD increment, 95% CI = 1.10-2.09), while further increases were associated with a marginally non-significant lower risk (HR = 0.80 per SD increment, 95% CI = 0.63-1.01), after full adjustment for potential confounders. In analyses of quartiles, CTX exhibited a similar inverted U-shaped relationship with incident fracture after adjustment, with a significant association observed only for the comparison of quartile 3 to quartile 1 (HR = 1.63, 95% CI = 1.10-2.43). In a subset with available measures, both OC and CTX were inversely associated with bone mineral density of the hip. CONCLUSION: CTX, but not OC, levels were associated with incident hip fracture in post-menopausal women, a relationship characterized by an inverted U-shape. These findings highlight the complex relationship of bone turnover markers with hip fracture risk.

History of cardiovascular disease and cardiovascular biomarkers are associated with 30-day mortality in patients with hip fracture.

Hip fractures are associated with increased mortality and it is important to identify risk factors. This study demonstrates that preexisting cardiovascular disease as well as cardiovascular biomarkers that are associated with increased 30-day mortality. These findings can be used to identify high-risk patients who might benefit from specialized care. INTRODUCTION: This study investigates the association between cardiovascular disease (CVD), cardiovascular biomarkers, and 30-day mortality following a hip fracture. METHODS: The Danish National Patient Registry was used to investigate the association between CVD and mortality following hip fracture in a nationwide population-based cohort study. In a subset of the included patients (n = 355), blood samples were available from a local biobank. These samples were used for analyzing the association between specific biochemical markers and mortality. The primary outcome was 30-day mortality. RESULTS: A total of 113,211 patients were included in the population-based cohort study. Among these, heart failure was present in 9.4%, ischemic heart disease in 15.9%, and ischemic stroke in 12.0%. Within 30 days after the hip fracture, 11,488 patients died, resulting in an overall 30-day mortality of 10.1%. The 30-day mortality was significantly increased in individuals with preexisting CVD with multivariably adjusted odds ratios of 1.69 (95% confidence interval, 1.60-1.78) for heart failure, 1.23 (1.17-1.29) for ischemic heart disease, and 1.06 (1.00-1.12) for ischemic stroke. In the local database including 355 patients, 41 (11.5%) died within 30 days. The multivariably adjusted odds ratio for 30-day mortality increased with increasing NT-proBNP (2.36 [1.53-3.64] per quartile) and decreased with increasing HDL cholesterol (0.58 [0.41-0.82] per quartile). On this basis, we established a model for predicting the probability of death based on the biochemical markers. CONCLUSION: Preexisting CVD was associated with increased 30-day mortality after a hip fracture. Furthermore, high levels of NT-proBNP and low levels of HDL cholesterol were associated with increased 30-day mortality.

Association of blood n-3 fatty acid with bone mass and bone marrow TRAP-5b in the elderly with and without hip fracture.

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment. INTRODUCTION: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples. METHODS: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44). RESULTS: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (ß = 0.615, P = 0.002) and total femur (ß = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (ß = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates. CONCLUSIONS: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.

The trajectory of C-reactive protein serum levels in older hip fracture patients with postoperative delirium.

OBJECTIVES: Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium. METHODS: This is a prospective cohort study of older patients undergoing acute surgery for hip fracture. Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C-reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5. RESULTS: Forty-one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1-2 days) and more prolonged delirium (3 days or more). CONCLUSIONS: Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory-vascular) pathological pathway of postoperative delirium.

The effect of intravenous iron on erythropoiesis in older people with hip fracture.

BACKGROUND: anaemia following hip fracture is common and associated with worse outcomes. Intravenous iron is a potential non-transfusion treatment for this anaemia and has been found to reduce transfusion rates in previous observational studies. There is good evidence for its use in elective surgical populations. OBJECTIVE: to examine the impact of intravenous iron on erythropoiesis following hip fracture. DESIGN: two-centre, assessor-blinded, randomised, controlled trial of patients with primary hip fracture and no contra-indications to intravenous iron. METHOD: the intervention group received three doses of 200 mg iron sucrose over 30 min (Venofer, Vifor Pharma, Bagshot Park, UK) on three separate days. Primary outcome was reticulocyte count at day 7 after randomisation. Secondary outcomes included haemoglobin concentration, complications and discharge destination. Eighty participants were randomised. RESULTS: there was a statistically significantly greater absolute final reticulocyte count in the iron group (89.4 (78.9-101.3) × 109 cells l-1 (n = 39) vs. the control (72.2 (63.9-86.4)) × 109 cells l-1 (n = 41); P = 0.019; (mean (95% confidence intervals) of log-transformed data). There were no differences in final haemoglobin concentration (99.9 (95.7-104.2) vs. 102.0 (98.7-105.3) P = 0.454) or transfusion requirements in the first week (11 (28%) vs. 12 (29%); P = 0.899). Functional and safety outcomes were not different between the groups. CONCLUSIONS: although intravenous iron does stimulate erythropoiesis following hip fracture in older people, the effect is too small and too late to affect transfusion rates. Trial Registry Numbers: ISRCTN:76424792; EuDRACT: 2011-003233-34.

High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes.

PURPOSE: Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM. METHODS: Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model. RESULTS: OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9-31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time. CONCLUSIONS: In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile.

Seasonality of hip fracture and vitamin D deficiency persists in a sub-tropical climate.

Both hip fractures and vitamin D (25-hydroxyvitamin D (25-OHD)) deficiency are more common in winter in regions with temperate climates, but few data exist for a sub-tropical climate. In a South East Queensland tertiary hospital over a 7-year period, there were significantly more hip fractures in winter than the other three seasons (analysis of variance P = 0.003), with associated higher frequency of 25-OHD deficiency - 42.5% in winter compared to 28.5% in summer, odds ratio 1.86 (95% confidence interval 1.35-2.56), P = 0.0001. Seasonality of hip fracture and 25-OHD deficiency occurs even in a sub-tropical climate.

Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men.

OBJECTIVE: Overt thyroid dysfunction is a risk factor for osteoporosis and fractures. Subclinical hyperthyroidism has also been associated with fracture. It remains unclear whether variation in thyroid hormones within the euthyroid range modulates bone health, particularly among older men. We assessed whether thyroid stimulating hormone (TSH) and free thyroxine (FT4) are associated with bone turnover markers (BTMs) and predict hip fracture risk in community-dwelling older men without known thyroid disease. DESIGN: Prospective cohort study. PATIENTS: Four thousand two hundred forty-eight men aged 70-89 years. MEASUREMENTS: Baseline blood samples were assayed for TSH, FT4, total osteocalcin (TOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (P1NP) and collagen type I C-terminal cross-linked telopeptide (CTX). Incidence of hip fracture events was ascertained to 2012. Associations of TSH and FT4 with BTMs were analysed at baseline using Pearson correlation coefficients, and with incident hip fracture using Cox proportional hazards regression. RESULTS: After excluding men with pre-existing thyroid or bone disease, there were 3, 338 men for analysis. Of these, 3, 117 were euthyroid, 135 had subclinical hypothyroidism, and 86 had subclinical hyperthyroidism. Men with subclinical thyroid disease were older, and those with subclinical hyperthyroidism had lower creatinine than the other groups. After multivariate analysis, there were no associations found between FT4, TSH or subclinical thyroid dysfunction and BTMs at baseline. Neither subclinical thyroid dysfunction, TSH nor FT4 were predictive of incident hip fracture in our study population. CONCLUSIONS: In euthyroid older men, TSH and FT4 were not associated with BTMs or incident hip fracture. Our findings differ from those previously described in postmenopausal women.

Sex hormone-binding globulin and risk of fracture in older adults: systematic review and meta-analysis of observational studies.

We conducted a meta-analysis of observational study to clarify the association between sex hormone-binding globulin (SHBG) levels and the risk of fracture in older adults. We found that higher SHBG levels were associated with an increased risk of fracture in older adults. INTRODUCTION: The association between SHBG levels and the risk of fracture in older adults remains elusive. We aim to clarify this association by conducting a meta-analysis of observational studies. METHODS: PubMed and Web of Science databases were searched for relevant observational studies investigating the association between SHBG levels and the risk of fracture in older adults. The relative risks (RRs) with 95% confidence intervals (CIs) from each study were transformed into a continuous variable for each 1 µg/dL increase in SHBG and were pooled under a random-effects model. RESULTS: A total of 16 observational studies were included in the present meta-analysis. The summary RR of fracture risk associated with each 1 µg/dL increase in SHBG was 1.18 (95% CI 1.11, 1.26); no statistically significant heterogeneity was observed across studies (I2 = 0%, P = 0.67). The positive association was also evident in men (RR 1.22, 95% CI 1.12, 1.33) and women (RR 1.15, 95% CI, 1.05, 1.26). By site of fracture, higher SHBG levels were positively associated with higher risks of hip fracture (RR 1.43, 95% CI 1.23, 1.65), vertebral fracture (RR 1.31, 95% CI 1.12, 1.54), and non-vertebral fracture (RR 1.21, 95% CI 1.06, 1.38). CONCLUSIONS: The present meta-analysis suggests that higher SHBG levels predict an increased risk of fracture in older adults. Further studies should aim to elucidate the complex biological mechanisms by which SHBG may affect fracture risk.