Differences In Fracture Incidence Research Articles

A simple fragility fracture risk score for type 2 diabetes patients: a derivation, validation, comparison, and risk stratification study.

The aims of this study were to develop and validate 2 simple scores for stratification of the risks of (1) any fragility (AF) and (2) major osteoporotic fracture (MOF) in type 2 diabetes (T2D) patients; we also compared the performance of these scores with that of the Fracture Risk Assessment Tool (FRAX) and its adjustments. In this longitudinal cohort study, 1855 patients with T2D were enrolled from January 2015 to August 2019. Cox proportional hazard regression was used to model the 5-year risk of AF and MOF. These scores were internally validated using a bootstrap resampling method of 1000. During a median follow-up of 5 years, 119 (6.42%) cases of AF and 92 (4.96%) cases of MOFs were identified. Both the concordance index (C-index) and calibration plots indicated improved identification performance using the newly established scores. Furthermore, these scores also showed improved outcomes regarding the decision curve analysis (DCA) and area under the curve (AUC) compared to the widely used FRAX and its derivatives. More importantly, these scores successfully separated T2D patients into risk groups according to significant differences in fracture incidence. These novel scores enable simple and reliable fracture risk stratification in T2D patients. Future work is needed to validate these findings in external cohort(s).

Incidence of Fractures after Intravenous Iron: A Retrospective Analysis Comparing Ferric Carboxymaltose and Ferric Derisomaltose

Background: Hypophosphatemia is a frequent side-effect of certain intravenous (i.v.) iron formulations, and a recent meta-analysis of prospective clinical trials reported that 54% of patients treated with ferric carboxymaltose (FCM) develop hypophosphatemia. While the incidence and time-course of hypophosphatemia are well known, the frequency of clinical consequences of these changes is poorly described. FCM infusions cause high intact fibroblast growth factor 23 (iFGF23), which is associated with hypophosphatemia, hyperphosphaturia, hypocalcitriolemia, hypocalcemia, secondary hypoparathyroidism, which is summarized as the ‘6H-syndrome’ that can ultimately result in osteomalacia. The association between treatment with FCM, high iFGF23, osteomalacia with fractures and nephrolithiasis is well documented in multiple case reports. This is not the case for ferric derisomaltose (FDI). Aims: The aim of the present study was to assess the incidence of fractures or radiological signs of osteomalacia and kidney stone in patients treated with FCM or FDI. Methods: Patients treated with FCM or FDI between January 2010 und December 2019 were identified by retrospective assessment of electronic health records of the University Hospital in Innsbruck, which is a large tertiary referral center in Western Austria. Dose, time of infusion, comorbidities and haematological parameters, serum iron parameters as well as markers of mineral metabolism were extracted from the healthcare records of each patient. Radiological and clinical endpoints included fractures, radiological signs of osteomalacia and kidney stone disease after the first infusion of FCM or FDI. The year before the first infusion was used as a control period. Results: In total, 289 patients were included and the median follow-up time was 5.8 years. Mean age was 44.6 years and 184 of 289 patients (64%) were females. In total 179 patients were treated with FCM and 110 patients received FDI. Grouping patients by drug revealed no differences in cumulative iron dose or number of drug applications. At baseline, serum creatinine was significantly lower in FDI-treated patients, but within the normal range for both groups. Mean hemoglobin concentrations were significantly lower in FCM-treated than in FDI-treated patients (95 g/L vs. 109 g/L) with no statistically significant differences in mean ferritin concentrations between groups at baseline. Assessment of treatment response 1-3 months after i.v. iron treatment showed a robust increase in hemoglobin and serum ferritin in both treatment groups. Baseline phosphate was significantly lower in FDI-treated patients with 3.07 mg/dL versus 3.34 mg/dL in the FCM treatment group. In FCM-treated patients a significantly greater change from baseline to 1-3 months after administration was found for phosphorous and calcium (Table 1). Hypophosphatemia was more commonly documented and more severe in FCM-treated patients, who also showed a significant increase in ALP. In a time to event analysis (fracture, osteomalacia and kidney stones) a significantly higher proportion of patients reached the combined endpoint in the FCM treatment group than in FDI-treated patients (Figure 1). Univariate Cox-regression for fractures after the infusion showed a HR of 4.54 for FCM treatment when compared to FDI (p=0.04). In contrast, no difference in fracture incidence was present in the year before the first iron infusion when both treatment groups were compared. Conclusions: In this retrospective analysis the combined event rate of fracture, radiological signs of osteomalacia and kidney stones was significantly higher among patients treated with FCM than after FDI treatment. This finding suggests that the observed changes in markers of mineral metabolism could indicate that FCM treatment is associated with a significantly higher risk of clinically relevant bone complications and kidney stone disease.

Effects of kidney tonic herbs for primary osteoporosis: A systematic review and meta-analysis.

Primary osteoporosis (POP) is one of the most common orthopedic conditions with a high risk of fractures. Effective treatment of POP is crucial for reducing disability rates and improving quality of life. Kidney tonic therapy is a classical traditional Chinese medicine approach for treating POP. This study aims to provide a comprehensive and reliable assessment of the clinical evidence of kidney tonic herbs (KTH) in treating POP patients. An extensive literature search was conducted in 8 electronic databases from their inception through September 30, 2022, to evaluate the efficacy and safety of KTH for POP. We included 43 randomized controlled trials with 4349 participants. The qualified studies will be chosen and evaluated separately by 2 researchers. The primary outcome measure was bone mineral density (BMD) of lumbar. RevMan 5.3 and Stata 16 were used to carry out the meta-analyses. Our meta-analysis showed 29 studies with significantly increased lumbar BMD (mean difference [MD] = 0.06; 95% confidence interval [CI]; I2 = 98%, P = .003), 18 studies with noticeably higher femoral neck BMD (MD = 0.08; 95% CI; I2 = 98%, P = .0005), 6 studies with significantly increased femoral trochanter BMD (MD = 0.10; 95% CI; I2 = 97%, P = .002), 4 studies with noticeably higher ward's triangle BMD (MD = 0.13; 95% CI; I2 = 100%, P = .04), and 3 studies with noticeably higher distal radius BMD (MD = 0.06; 95% CI; I2 = 86%, P = .009). One study showed 12 falls and 8 fallers in the intervention group, 28 falls and 17 fallers in the control group at 36 months. 3 studies showed a significant difference in fracture incidence between the intervention group and the control group (95% CI: 0.15-0.81; I2 = 0%, P = .01). Additionally, the meta-analysis demonstrated that KTH offered superior pain relief (8 trials, n = 980; 95% CI: -1.05 to -0.74; I2 = 94%, P < .00001). Besides, KTH found no serious harmful effects. KTH may increase BMD and decrease the likelihood of fractures in POP patients. However, further research is necessary to investigate the effectiveness of KTH in reducing falls and fractures.

The clinical utility of the BMD-related comprehensive genome-wide polygenic score in identifying individuals with a high risk of osteoporotic fractures.

This study sought to construct genome-wide polygenic scores for femoral neck and total body BMD and to estimate their potential in identifying individuals with a high risk of osteoporotic fractures. Genome-wide polygenic scores were developed and validated for femoral neck and total body BMD. We externally tested the PGSs, both by themselves and in combination with available clinical risk factors, in 455,663 European ancestry individuals from the UK Biobank. The predictive accuracy of the developed genome-wide PGS was also compared with previously published restricted PGS employed in fracture risk assessment. For each unit decrease in PGSs, the genome-wide PGSs were associated with up to 1.17-fold increased fracture risk. Out of four studied PGSs, [Formula: see text] (HR: 1.03; 95%CI 1.01-1.05, p = 0.001) had the weakest and the [Formula: see text] (HR: 1.17; 95%CI 1.15-1.19, p < 0.0001) had the strongest association with an incident fracture. In the reclassification analysis, compared to the FRAX base model, the models with [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] improved the reclassification of fracture by 1.2% (95% CI, 1.0 to 1.3%), 0.2% (95% CI, 0.1 to 0.3%), 1.4% (95% CI, 1.3 to 1.5%), and 2.2% (95% CI, 2.1 to 2.4%), respectively. Our findings suggested that an efficient PGS estimate enables the identification of strata with up to a 1.7-fold difference in fracture incidence. Incorporating PGS information into clinical diagnosis is anticipated to increase the benefits of screening programs at the population level.

Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials.

IntroductionVitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women.MethodsWe searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria.ResultsSixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) (P = 0.006) with VK2. The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 (P = 0.03). The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65). However, after excluding one heterogeneous study, the overall effect test showed a significant reduction in fracture incidence with VK2 (RR = 0.43, P = 0.01). In addition, this meta-analysis showed that VK2 reduced serum undercarboxylated osteocalcin (uc-OC) levels and the ratio of uc-OC to cOC in both subgroups of VK2 combined intervention and alone. However, for carboxylated osteocalcin (cOC), both subgroup analysis and overall effect test showed no significant effect of VK2 on it. And the pooled analysis of adverse reactions showed no significant difference between the VK2 and control groups (RR = 1.03, 95%CI 0.87 to 1.21, P = 0.76).ConclusionsThe results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength.

Inflammatory status, body composition and ethnic differences in bone mineral density: The Southall and Brent Revisited Study.

Ethnic differences in bone mineral density (BMD) and fracture risk are well-described; the aim of this study was to investigate whether central adiposity or inflammatory status contribute to these ethnic differences in BMD in later life.The Southall and Brent Revisited study (SABRE) is a UK-based tri-ethnic cohort of men and women of European, South Asian or African Caribbean origin. At the most recent SABRE follow-up (2014–2018), in addition to measures of cardiometabolic phenotype, participants had dual-energy X-ray absorptiometry (DXA) bone and body composition scans. Multiple linear regression was used to determine whether markers of body composition, central adiposity or inflammatory status contributed to ethnic differences in BMD.In men and women, age- and height-adjusted BMD at all sites was higher in African Caribbeans compared to Europeans (femoral neck: standardised β (95% confidence interval): men: 1.00SD (0.75, 1.25); women: 0.77SD (0.56, 0.99)). South Asian men had higher BMD than European men at the hip (femoral neck: 0.34SD (95%CI: 0.15, 0.54)). Although adjustment for body mass index (BMI) or lean mass index (LMI) at the lumbar spine reduced the size of the difference in BMD between African Caribbean and European men (age and height adjusted difference: 0.35SD (0.08, 0.62); age and BMI adjusted difference: 0.25SD (−0.02, 0.51)), in both men and women ethnic differences remained after adjustment for measures of central adiposity (estimated visceral adipose tissue mass (VAT mass) and android to gynoid ratio) and inflammation (interleukin-6 (logIL-6) and C-reactive protein (logCRP)). Furthermore, in women, we observed ethnic differences in the relationship between BMI (overall interaction: p = 0.04), LMI (p = 0.04) or VAT mass (p = 0.009) and standardised lumbar spine BMD.In this tri-ethnic cohort, ethnic differences in BMD at the femoral neck, total hip or lumbar spine were not explained by BMI, central adiposity or inflammatory status. Given ethnic differences in fracture incidence, it is important to further investigate why ethnic differences in BMD exist.

Contribution of elevation and residential proximity to the coast in explaining geographic variations in hip fracture incidence. A Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) study.

Norway is an elongated country extending north of the Arctic Circle with substantial coast-inland variation in topography and climate. Differences in hip fracture incidence between counties and a distinct seasonal variation have previously been shown. The aim of the current study was to explore these variations further by considering associations of height above sea level (elevation) and distance to the coast with hip fracture incidence. All patients with hip fractures admitted to Norwegian hospitals in the period 2009-2018 were included. Individual residential elevation and distance to the coast was calculated in Geographic Information Systems and combined with individual-level population data on all Norwegians 50years of age or older during the observation period, including hospital information on fractures. Age-standardized incidences rate and incidence rate ratios with 95% confidence intervals (IRR, 95% CI) according to elevation and coastal proximity were estimated. The associations were tested using Poisson models adjusting for sex, urban/rural location of residency, country of birth, and season of hip fracture occurrence. From 2009 to 2018, there were 85,776 first hip fractures. There was an increasing risk with higher residential elevation (above versus below mean) for women: IRR = 1.04, 95% CI: 1.02, 1.05), but not for men (IRR = 1.00, 95% CI: 0.97, 1.02). Incidence of hip fracture increased with distance from the coast. Women residing the farthest away from the coast (above versus below mean distance) had a higher age-adjusted incidence of hip fracture compared to those living closer to the coast (IRR = 1.04 (95% CI: 1.02, 1.06), whereas no association was found in men (IRR = 1.00 (95% CI: 1.00, 1.01). Combining elevation and distance to coast showed a higher incidence in women living at high elevation far from the coast compared with women living at low elevation near the coast (IRR = 1.07, 95% CI: 1.04, 1.10). A similar result was found in men but only for hip fractures occurring during March-May (IRR = 1.07, 95% CI: 1.00, 1.15). The previously shown patterns of county differences and seasonal variations were unchanged when considering geography. We found a somewhat higher incidence of hip fracture in inland residents living in areas of high elevation, as compared to those living in more coastal proximity; however, the geographic variation did not explain county and seasonal differences in fracture incidence in Norway. More in-depth analyses on temperature and climate factors may give further clues.

SUN-065 Bone Health Outcomes in a Large, Diverse Pediatric Cohort Undergoing Hematopoietic Stem Cell Transplant

Background:Impaired bone mineral density (BMD) is a known complication of hematopoietic stem cell transplantation (HSCT) in adults and may lead to increased fracture risk. Little is known in pediatrics about the risks for impaired BMD and fragility (low trauma) fractures after HSCT. Factors that may influence the risk of bone disease include underlying diagnosis, glucocorticoid exposure, and HSCT complications (e.g. graft versus host disease (GVHD)). Our study aims to describe the incidence of fragility fractures in a large diverse pediatric HSCT population and to identify risk factors of both fracture and impaired BMD.Methods:We reviewed the records of 237 patients (age ≤ 21 years at time of transplant) who underwent HSCT at our institution between January 2015 and March 2018. The primary endpoint was incidence of fragility fractures and the secondary endpoint was assessment of BMD on dual-energy X-ray absorptiometry (DXA). We analyzed DXA results at one-year post-HSCT in 72 out of 206 patients alive at 1 year.Results:There were 25/237 (10.5%) patients with evidence of fragility fracture on x-ray. Of those, 18/25 (72%) were spine fractures. For patients who had fractures, median time to fracture was 5.9 months after BMT. Mortality at one-year was proportionally higher, though not significant (p=0.11) in patients who had at least one fragility fracture (24%; 6/25) compared to patients without fragility fracture (12%; 25/212). Vitamin D status at one-year post transplant was sufficient (>20ng/mL) in 94% (160/171) of patients measured. There was no difference in incidence of fracture between vitamin D sufficient and insufficient patients. The median height-for-age adjusted Z-score (HAZ) for spine BMD at one-year post transplant was 0.13 in all patients. The median HAZ spine BMD Z-score in patients with fragility fracture was -1.64, though data was available for only 5 patients.Conclusions:The incidence of fragility fractures, especially vertebral compression fractures, after pediatric HSCT is striking and is higher than in adult populations. Furthermore, there are likely additional asymptomatic patients with occult fractures not detected in out cohort. Additional analysis will assess the associations between underlying medical diagnosis, GVHD, and chronic glucocorticoid exposure on fragility fracture risk. The high incidence of fragility fractures seen in this study advocates for establishing bone health screening protocols with attention toward spinal imaging in pediatric patients undergoing HSCT.

Glycemic control and 10-year odds of all-cause fractures in elderly veterans with type 2 diabetes

AimsTo investigate the relationship of average level of glycemic control and fractures in elderly Veterans. MethodsRetrospective cohort of Veterans (age ≥65) grouped as follows: no diabetes, HbA1c ≤7.0% [≤53 mmol/mol], HbA1c 7.1–8.0% [54–64 mmol/mol], HbA1c 8.1–9.0% [65–75 mmol/mol], and HbA1c >9% [>75 mmol/mol]. Data from January 1, 2010 – January 1, 2017 from the Veteran’s Affairs Corporate Data Warehouse was analyzed using Chi-square and Cox regression analysis. Results3434 fractures occurred from the 36,744 Veterans included. The fracture incidences were 14.4, 11.7, 7.9, 8.2, and 10.8 events per 1000 patient years and the hazard ratios were 1.233 (1.130–1.345); p < 0.0001, 0.718 (0.626–0.825); p < 0.0001, 0.682 (0.545–0.854); p = 0.0009, and 0.887 (0.633–1.245); p = 0.4915 in the no diabetes, HA1c ≤7% [≤53 mmol/mol], 7.1–8% [54–64 mmol/mol], 8.1–9% [65–75 mmol/mol], and >9% [>75 mmol/mol] groups after accounting for covariates in the final model. ConclusionIn elderly Veterans with type 2 diabetes the average HbA1c 7.1–8.0% [54–64 mmol/mol], and 8.1–9% [65–75 mmol/mol] have the lowest fracture incidence and those without diabetes showing the highest incidence rate; however, due to the overall low rate of fracture, the absolute difference in incidence of fracture was very small at 2–5 per 1000 patient years. Beyond limiting the risk factors identified these results don’t support altering diabetes treatment goals to reduce fracture risk.

Differences in Fracture Incidence According to Caregiver Type in Stroke Survivors

BackgroundTo assess whether the type of primary caregiver is a risk factor of the incidence of fracture among older adults who have survived a stroke. MethodsData from 4282 stroke survivors in the National Health Insurance Service—Senior Cohort (2002-2013) were used in this study. We categorized type of primary caregiver as none, spouse/family caregiver, and formal caregiver. The incidence of fracture within the year postdischarge was used as the outcome variable. These data were subjected to a survival analysis using the Cox proportional hazard model. ResultsOf the 4282 stroke survivors, 308 (7.2%) experienced a fracture during the 1-year follow-up period. According to type of primary caregiver, the adjusted hazard ratio (HR) of fracture was lower among those whose caregiver was a spouse (HR = .68, 95% confidence interval [CI], .48-.96] and those with a formal caregiver (HR = .59, 95% CI, .36-.97) compared to stroke survivors with no caregiver. In particular, those with a family or formal caregiver who were being cared for in nursing facilities were less likely to be associated with fracture than those with no caregiver. ConclusionsThe adjusted HR of fracture among stroke survivors was lower among those with primary caregivers compared to those without them. Thus, the government should monitor and allocate the appropriate attention to stroke survivors after discharge in order to ensure that they obtain the needed health care, especially for stroke survivors who are without a primary caregiver.

Mild Traumatic Brain Injury in Adolescent Mice Alters Skull Bone Properties to Influence a Subsequent Brain Impact at Adulthood: A Pilot Study.

Mild traumatic brain injuries (mTBI) are common during adolescence, and limited clinical evidence suggests that a younger age at first exposure to a mTBI may lead to worse long-term outcomes. In this study, we hypothesized that a mTBI during adolescence would predispose toward poorer neurobehavioral and neuropathological outcomes after a subsequent injury at adulthood. Mice received a mild weight drop injury (mTBI) at adolescence (postnatal day 35; P35) and/or at adulthood (P70). Mice were randomized to 6 groups: ‘sham’ (sham-surgery at P35 only); ‘P35’ (mTBI at P35 only); ‘P35 + sham’ (mTBI at P35 + sham at P70); ‘sham + P70’ (sham at P35 + mTBI at P70); ‘sham + sham’ (sham at both P35 and P70); or ‘P35 + P70’ (mTBI at both P35 and P70). Acute apnea and an extended righting reflex time confirmed a mTBI injury at P35 and/or P70. Cognitive, psychosocial, and sensorimotor function was assessed over 1-week post-injury. Injured groups performed similarly to sham controls across all tasks. Immunofluorescence staining at 1 week detected an increase in glial activation markers in Sham + P70 brains only. Strikingly, 63% of Sham + P70 mice exhibited a skull fracture at impact, compared to 13% of P35 + P70 mice. Micro computed tomography of parietal skull bones found that a mTBI at P35 resulted in increased bone volume and strength, which may account for the difference in fracture incidence. In summary, a single mTBI to the adolescent mouse brain did not exacerbate the cerebral effects of a subsequent mTBI in adulthood. However, the head impact at P35 induced significant changes in skull bone structure and integrity. These novel findings support future investigation into the consequences of mTBI on skull bone.

An increased rate of fracture occurs a decade earlier in HIV+ compared with HIV- men.

To determine the incidence of fracture among aging HIV-infected (HIV+) and uninfected men (HIV-). To evaluate factors independently associated with fracture risk. Prospective, multicenter cohort study of men with or at risk for HIV. Outcome measures: all fractures (excluding skull, face and digits) and fragility fractures (vertebral column, femur, wrist and humerus) were collected semiannually in 1221 HIV+ and 1408 HIV- men aged at least 40. Adjusted incident rate ratios (aIRR) with an interaction term for age (40-49, 50-59 and ≥60 years) and HIV serostatus were estimated with Poisson regression models accounting for additional risk factors. Fracture incidence increased with age among both HIV+ and HIV- men. Although there was no significant difference in fracture incidence by HIV serostatus among men aged 40-49 years, the HIV+ men aged 50-59 years had a significantly higher incidence of all fractures [aIRR: 2.06 (1.49, 2.84)] and fragility fractures [aIRR: 2.06 (1.21, 3.50)] compared with HIV- participants of similar age. HIV modified the effect of age on all fractures (P = 0.002) but did not significantly modify the effect for fragility fractures (P = 0.135). Hypertension increased the rate of all fractures by 32% after adjustment for covariates [aIRR: 1.32 (1.04, 1.69)]. Fracture incidence increased with age among HIV+ and HIV- men but was higher among HIV+ men. A significant increase in fracture incidence was found among 50-59-year-old HIV+ men, highlighting the importance of osteoporosis screening for HIV-infected men above the age of 50.

Outcomes of bisphosphonate therapy in kidney transplant recipients: a systematic review and meta-analysis.

Mineral and bone disorders that precede kidney transplantation are exacerbated in the post-transplant setting by tertiary hyperparathyroidism and immunosuppressive regimens. Bone mineral density (BMD) decreases following transplantation, leading to increased fracture risk. The effect of bisphosphonates on fracture is unknown. The aim of this study was to update estimates of change in BMD and fracture rates in bisphosphonate-treated kidney transplant recipients through meta-analysis. Studies comparing bisphosphonate therapy to standard of care were included if follow-up duration was more than 6months. We performed random-effects meta-analysis to determine the effect of bisphosphonates on lumbar spine and femoral neck BMD and fracture rates. Bisphosphonates improved femoral neck and lumbar spine BMD compared with controls (0.055g/cm(2) , 95% CI 0.012-0.099 and 0.053g/cm(2) , 95% CI 0.032-0.074, respectively) without adversely affecting serum creatinine or calcium. This corresponded to an unweighted improvement in BMD of 6.0% and 7.4%, respectively. There was no difference in fracture incidence in the two groups. Bisphosphonate therapy in kidney transplant recipients is associated with a statistically significant improvement in BMD at the lumbar spine and femoral neck. There was no difference in fracture incidence. Bisphosphonates did not adversely affect allograft dysfunction or serum calcium levels.

State of origin: Australian states use widely different resources for hospital management of hip fracture, but achieve similar outcomes.

Objective Hospital management of hip fracture varies widely with regard to length of stay, delivery of post-surgical care and costs. The present study compares the association between hospital utilisation and costs and patient outcomes in the six Australian states. Methods The present study was a retrospective cohort study of linked administrative databases for 2530 Australian veterans and war widows aged ≥65 years, hospitalised for hip fracture in 2008-09. Department of Veterans' Affairs datasets for hospital episodes, residential aged care admissions and date of death were linked. Patient characteristics, hospital utilisation and process data, rates of mortality and residential care placement and delivery of community services were compared for patients from each of the states. Results There were no significant differences in fracture incidence, patient demographics or fracture type among the states. Adjusted total mean length of hospital stay ranged from 24.7 days (95% confidence interval (CI) 22.3-27.5 days) to 35.0 days (95% CI 32.6-37.6 days; P<0.001) and adjusted total hospital cost ranged between A$24792 (95% CI A$22191-A$27700) and A$35494 (95% CI A$32853-A$38343; P<0.001). Rates of referral to rehabilitation ranged from 31.7% to 50.4% (P=0.003). At 1 year, there were no significant differences between states for key outcome determinants of mortality (P=0.71) or for the proportion of patients who retained their independent living status (P=0.66). Conclusion Hospital resources for management of hip fracture differ substantially among the Australian states. Key medium-term patient outcomes do not show significant differences. A potential for substantial cost-efficiencies without increased risk to patient welfare is suggested. What is known about this topic? Hospital resources deployed in the initial management of hip fracture differ widely between countries, regions and individual hospitals. Patient outcomes also vary widely, but are inconsistently associated with resource outlays. What does this paper add? The paper describes the different resource outlays for management of hip fracture in six Australian jurisdictions and the absence of equivalent differences in medium-term patient outcomes. What are the implications for practitioners? Efficiencies in hospital management of hip fracture may be achievable without negative consequences for patients. The elements of models of care should be examined for their contribution to early and later patient outcomes.

Anabolic and antiresorptive therapy for osteoporosis: combination and sequential approaches.

In the recent Bone Key Reports review, it was noted that combinations of anabolic and antiresorptive agents have potential to improve bone density and bone strength more than either agent as monotherapy. Small clinical trials have been performed evaluating combinations of PTH1-34 (TPTD) or PTH1-84 (PTH) with a variety of antiresorptives including hormone/estrogen therapy, raloxifene, alendronate, risedronate, ibandronate, zoledronic acid, and denosumab. Most of the studies evaluate dual-energy X-ray absorptiometry outcomes, and a few trials report volumetric mineral density (BMD) by quantitative computed tomography, followed by finite element modeling to calculate bone strength. None of the studies has been powered to assess differences in fracture incidence between combination therapy and monotherapy. BMD outcomes vary based on the timing of introduction of the anabolic agent (before, during, or after antiresorptive treatment), as well as the specific anabolic and antiresorptive used. Furthermore, effects of combination therapies are site-dependent. The most consistent effect of combining antiresorptive agents with PTH or TPTD is a superior hip BMD outcome compared with TPTD/PTH alone. This is most evident when TPTD/PTH is combined with a bisphosphonate or denosumab. In contrast to findings in the hip, in the majority of studies, there is no benefit to spine BMD with combination therapy vs monotherapy. The 2 exceptions to this are when TPTD is combined with denosumab and when TPTD is given as monotherapy first for 9 months, followed by the addition of alendronate (with continuation administration of TPTD). Based on what we now know, in patients previously treated with bisphosphonates who suffer hip fractures or who have very low or declining hip BMD, strong consideration should be given to starting TPTD and continuing a potent antiresorptive agent (possibly switching to zoledronic acid or denosumab) to improve hip BMD and strength quickly. Furthermore, in treatment naïve individuals with very severe osteoporosis, such as those with spine and hip fractures, combination therapy with TPTD and denosumab or TPTD followed by combination treatment with a potent bisphosphonate or denosumab should be considered to maximize early increases in BMD throughout the skeleton (Cosman BoneKEy Rep 3, 2014).

Combination therapy for osteoporosis: a reappraisal.

Combinations of anabolic and antiresorptive agents have potential to improve bone density and bone strength more than either agent alone. A large number of relatively small clinical trials have been performed evaluating combinations of PTH1-34 or PTH1-84 with a variety of antiresorptives, including hormone/estrogen therapy, raloxifene, alendronate (Aln), risedronate, ibandronate, zoledronic acid and denosumab (Dmab). Most of the studies evaluate dual-X-ray densitometry outcomes, with a few trials reporting volumetric bone mineral density (BMD) by quantitative computed tomography followed by finite element modeling of bone strength. None of the studies has been powered to assess differences in fracture incidence between combination therapy and monotherapy. BMD outcomes vary depending on the timing of introduction of the anabolic agent (before, during or after antiresorptive treatment), as well as according to the specific anabolic and antiresorptive used. Furthermore, effects of combination therapies are site dependent. The most consistent effect of combining antiresorptive agents with parathyroid hormone (PTH) is a superior hip BMD outcome compared with PTH alone. This is most evident when PTH is combined with a bisphosphonate or Dmab. In contrast to findings in the hip, in the majority of studies there is no benefit to spine BMD with combination therapy when compared with monotherapy. The two exceptions to this are when PTH is combined with Dmab and when PTH is given as monotherapy first for 9 months followed by the addition of Aln and continuation of PTH as combination treatment. On the basis of what we now know, in patients on bisphosphonates who suffer hip fractures or who have very low hip BMD, strong consideration should be given to starting teriparatide and continuing a bisphosphonate (possibly switching to zoledronic acid or even Dmab) to maximize hip BMD and strength. Furthermore, in treatment-naive individuals with very severe osteoporosis, such as those with spine and hip fractures, combination therapy with PTH and Dmab or PTH followed by combination treatment with a potent bisphosphonate or Dmab should be considered to maximize early increases in BMD.

Role and significance of dual-energy X-ray absorptiometry in measurement of bone mineral density in children with upper extremity fractures

Objective To measure the bone mineral density in children with dual-energy X-ray absorptiometry and examine the relevance of bone mineral density with the risk of pediatric upper limb fracture.Methods A total of 864 children (8-14 years of age) admitted into our hospital in 2009 were involved in the study.The bone mass density (Z score) at the left radius was measured using dual-energy X-ray absorptiometry.Children were grouped according to their Z score and age to observe correlations of Z value and age with the incidence of fractures.Results Thirty-three children were lost to follow-up.For the other 831 children,the mean duration of follow-up was 2 years.Z sore was ≤-2 in 66 children and ＞-2 in 765 children.There was significant difference in fracture incidence between children with Z score of ≤-2 and ＞-2 (27.27％ vs 5.49％,P ＜0.01).Furthermore,fracture incidence in children at age group of 8-10 years and 11-14 years revealed significant difference (10.83％ vs 5.03％,P ＜ 0.01).Conclusions Bone mineral density is closely related to upper limb fracture in children and increases with aging.Early application of dual-energy X-ray absorptiometry to detect the bone density is an effective primary measure for prevention of fractures in children. Key words: Bone density ; Upper extremity; Child

Exposure to Proton Pump Inhibitors is a Risk Factor for New Fractures in Hepatitis C Patients Following IFN/Ribavirin Therapy Irrespective of Virological Response

Purpose: Overall incidence of bone fractures among HCV positive patients is higher in those who receive proton pump inhibitors (PPI) than in those who do not receive PPI. The purpose of this study is to determine whether the increased bone fracture incidence in hepatitis C patients associated with PPI is dependent upon viral clearance. Methods: A retrospective cohort study of the incidence of bone fractures after treatment with interferon/ribavirin (IFN/RIB) based therapy treated between 1/1999 and 1/2011 in 365 HCV antibody positive veterans was performed. The primary study endpoints were the number of bone fractures after therapy in HCV patients with a response (R), defined as an SVR or end of treatment response (ETR) or those with NR (defined as nonresponder or relapser). For both HCV groups (R and NR), the beginning and final date of the bone fracture observation period was defined as 6 months after IFN/RIB therapy and the study end date, respectively. Body mass index (BMI), calcium levels, ethnicity, tobacco, alcohol and PPI use were collected. Statistical differences in fracture incidence between groups were determined by Mann Whitney U and multivariable regression analysis. Results: Our cohort was 92.3% male, 70% W, 26% AA and 2% H with a mean age of 57.7 yrs. Response occurred in 44% of HCV patients, with significantly more AA in NR than R (34% vs 13%) but with no differences between groups in BMI, calcium levels, gender, alcohol, and PPI use. Among the study population with complete data analyzed (n=342), similar number of fractures were noted after IFN/RIB therapy in NR (n=7) and R (n=6) groups. After adjusting for ethnicity, gender, BMI, alcohol, tobacco and PPI use, there was no difference in new bone fracture incidence between R and NR in patients with chronic HCV. Of interest, more PPI users had fractures post IFN/Rib therapy than non PPI users (p = 0.003). Conclusion: In patients with chronic HCV, SVR did not confer a decreased risk of new bone fractures. Importantly, PPI were a risk factor for new fractures in Hepatitis C patients after IFN/Ribavirin therapy,irrespective of Hepatitis C viral clearance.

Implant-related Fractures in Children

To our knowledge, there are no comprehensive clinical studies of implant-related fractures in children. Our goal was to identify the incidence, skeletal location, and associated diagnoses of implant-related fractures. We reviewed our institutional database to identify cases of implant insertion (7584 cases) in patients less than 18 years old from January 1, 1995 through December 31, 2009. We calculated the overall incidence of these fractures and stratified the incidence by skeletal location and preoperative diagnoses. Fisher exact test was used to ascertain differences in fracture incidence. Risk ratios were calculated when appropriate. Significance was set at P<0.05. There were 25 cases of implant-related fractures: 22 in the femur, 2 in the tibia, and 1 in the radius. The overall incidence of implant-related fracture was 0.33%; the incidence by skeletal location was: femur, 0.89%; tibia, 0.1%; and radius, 0.14%. Associated diagnoses were cerebral palsy (9 cases), hip dysplasia (3 cases), spina bifida (2 cases), and avascular necrosis (1 case); 10 cases were associated with "other diagnoses," which included various skeletal syndromes (5 cases) and traumatic fractures (5 cases). The incidences of implant-related fractures by diagnoses were: cerebral palsy, 1.1%; hip dysplasia, 1.1%; spina bifida, 1.3%; and avascular necrosis, 0.35%. The incidence of implant-related fracture in the "other diagnoses" group was 0.16%, and the incidence of fracture in otherwise healthy patients was 0.084%. The femur was 15.2 times more likely to fracture than other bones (P<0.001). Diagnoses of cerebral palsy, hip dysplasia, spina bifida, and avascular necrosis were 6.1 times more likely to be associated with implant-related fractures than the "other diagnoses" (P<0.001). The mean time to fracture in the study was 2.8 years. The overall implant removal rate at our institution was 24.3%, and it varied significantly by patient diagnosis (P<0.01). Skeletal location and preoperative diagnosis should be factors of consideration in a surgeon's decision about removing implants to prevent implant-related fractures. Prognostic Level III.

Proton Pump Inhibitors Increase the Incidence of Bone Fractures in Hepatitis C Patients

While proton pump inhibitors (PPI) may increase the risk of bone fractures, the incidence of new bone fractures in a chronic hepatitis C virus (HCV) infected cohort, with or without PPI exposure, has not been explored. A retrospective cohort study of the incidence of bone fractures over 10 years in 9,437 HCV antibody positive patients in the Dallas VA Hepatitis C Registry was performed. The study endpoint was the incidence of verified new bone fractures per patient-years (pt-yrs) in PPI users compared to non-PPI users. PPI use was defined as those taking a PPI for ≥360 days. Pt-yrs of exposure for PPI users began on the first PPI prescription date, and pt-yrs of exposure for non-PPI users began with first date of any non-PPI prescription. For both HCV groups, the final date of patients' study duration was defined by end of PPI exposure, bone fracture occurrence, death or end of study evaluation period. Exclusion criteria included use of bone health modifying medications ≥30 days. Statistical differences in fracture incidence between groups were determined by multivariate regression analysis. Among the total study population analyzed (n = 2,573), 109 bone fractures occurred. Unadjusted bone fracture incidences were 13.99/1,000 pt-yrs vs. 5.86/1,000 pt-yrs in PPI and non-PPI users, respectively. The adjusted hazard ratio for new bone fractures was 3.87 (95 % CI 2.46-6.08) (p < 0.001) in PPI users. In patients with chronic HCV, use of PPI for >1 year increased the risk of new bone fractures by more than threefold.