Re-evaluating the Use of High Sensitivity Troponin to Diagnose Blunt Cardiac Injury.

INTRODUCTION: Blunt cardiac injury (BCI) can be challenging diagnostically, and if misdiagnosed, can lead to life-threatening complications. Our institution previously evaluated BCI screening with troponin and electrocardiogram (EKG) during a transition from troponin I to high sensitivity troponin (hsTnI), a more sensitive troponin I assay. The previous study found an hsTnI of 76 ng/L had the highest capability of accurately diagnosing a clinically significant BCI. The aim of this study was to determine the efficacy of the newly implemented protocol. METHODS: Patients diagnosed with a sternal fracture from March 2022 to April 2023 at our urban level-1 trauma center were retrospectively reviewed for EKG findings, hsTnI trend, echocardiogram changes, and clinical outcomes. The BCI cohort and non-BCI cohort ordinal measures were compared using Wilcoxon's two-tailed rank sum test and categorical measures were compared with Fisher's exact test. Youden indices were used to evaluate hsTnI sensitivity and specificity. RESULTS: Sternal fractures were identified in 206 patients, of which 183 underwent BCI screening. Of those screened, 103 underwent echocardiogram, 28 were diagnosed with clinically significant BCIs, and 15 received intervention. The peak hsTnI threshold of 76 ng/L was found to have a Youden index of 0.31. Rather, the Youden index was highest at 0.50 at 40 ng/L (sensitivity 0.79 and specificity 0.71) for clinically significant BCI. CONCLUSIONS: Screening patients with sternal fractures for BCI using hsTnI and EKG remains effective. To optimize the hsTnI threshold, this study determined the hsTnI threshold should be lowered to 40 ng/L. Further improvements to the institutional protocol may be derived from multicenter analysis.

Circulating Hsa-miR499a-5p as markers in dysmobility syndrome patients: a new index for diagnosing dysmobility syndrome based on osteoporosis and predicting fracture risk.

BACKGROUND: Dysmobility syndrome based on osteoporosis (ODS) is a disease characterized by low bone mass and low muscle mass. Its features are high fracture and high fall risk. Falls and fractures are the most important factors affecting the quality of life and lifespan of ODS. However, there is no serum marker for the evaluation of ODS patients.Our previous studies have shown that the expression of circulating miRNA is stable and is a good marker for disease diagnosis. Therefore, this study aims to explore potential serum markers of ODS. METHODS: A total of 78 subjects were included in this study. The data including appendicular skeletal muscle mass index, bone mineral density, bone metabolism markers, and other relevant information were collected for analysis. Real-time quantitative polymerase chain reaction was used to detect 19 miRNAs associated with muscle mass reduction. The correlation of quantitative data was analyzed by Pearson. The receiver operating characteristic curve was used to evaluate the performance of miRNA as a biomarker. RESULTS: In this study, we found that the muscle mass and strength of patients with ODS are significantly reduced and are negatively correlated with the risk of fracture. The hsa-miR-499a-5p is specifically downregulated in ODS, and is positively correlated with muscle mass and strength, and negatively correlated with the risk of fracture. Compared with muscle mass and strength, hsa-miR-499a-5p has better sensitivity and specificity as a diagnostic marker. CONCLUSION: hsa-miR-499a-5p is a potential serum biomarker for assessing muscle function and predicting fall or fracture risk in the ODS population.

Influence of serum uric acid on bone and fracture risk in postmenopausal women.

AIMS: Uric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture. METHODS: An observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray. RESULTS: Higher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures. CONCLUSIONS: In the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures.

Association between preoperative lactate level and early complications after surgery for isolated extremity fracture.

BACKGROUND: The role of lactate level in selecting the timing of definitive surgery for isolated extremity fracture remains unclear. Therefore, we aimed to elucidate the use of preoperative lactate level for predicting early postoperative complications. METHODS: This was a single-center retrospective observational study of patients with isolated extremity fracture who underwent orthopedic surgery. Patients who underwent lactate level assessment within 24 h prior to surgery were included. The incidence of early postoperative complications was compared between patients with a preoperative lactate level of ≥ 2 and < 2 mmol/L. Moreover, subgroup analyses were performed based on the time from hospital arrival to surgery and fracture type. RESULTS: In total, 187 patients were included in the study. The incidence of postoperative complications was significantly higher in patients with a preoperative lactate level of ≥ 2 mmol/L than those with a preoperative lactate level of < 2 mmol/L. This result did not change after adjusting for age and severity. Further, a high preoperative lactate level was associated with a greater incidence of postoperative complications in patients who underwent definitive surgery within 6 h after arrival. CONCLUSION: A preoperative lactate level of ≥ 2 mmol/L was associated with a greater incidence of early postoperative complications in isolated extremity fractures. Nevertheless, this correlation was only observed among patients who underwent definitive fixation within 6 h after hospital arrival.

Clinical, biochemical and genetic findings in adult patients with chronic hypophosphatasemia.

PURPOSE: The study aimed to define the clinical, biochemical and genetic features of adult patients with osteopenia/osteoporosis and/or bone fragility and low serum alkaline phosphatase (sALP). METHODS: Twenty-two patients with at least two sALP values below the reference range were retrospectively enrolled after exclusion of secondary causes. Data about clinical features, mineral and bone markers, serum pyridoxal-5'-phosphate (PLP), urine phosphoethanolamine (PEA), lumbar and femur bone densitometry, and column X-ray were collected. Peripheral blood DNA of each participant was analyzed to detect ALPL gene anomalies. RESULTS: Pathogenic ALPL variants (pALPL) occurred in 23% and benign variants in 36% of patients (bALPL), while nine patients harbored wild-type alleles (wtALPL). Fragility fractures and dental anomalies were more frequent in patients harboring pALPL and bALPL than in wtALPL patients. Of note, wtALPL patients comprised women treated with tamoxifen for hormone-sensitive breast cancer. Mineral and bone markers were similar in the three groups. Mean urine PEA levels were significantly higher in patients harboring pALPL than those detected in patients harboring bALPL and wtALPL; by contrast, serum PLP levels were similar in the three groups. A 6-points score, considering clinical and biochemical features, was predictive of pALPL detection [P = 0.060, OR 1.92 (95% CI 0.972, 3.794)], and more significantly of pALPL or bALPL [P = 0.025, OR 14.33 (95% CI 1.401, 14.605)]. CONCLUSION: In osteopenic/osteoporotic patients, single clinical or biochemical factors did not distinguish hypophosphatasemic patients harboring pALPL or bALPL from those harboring wtALPL. Occurrence of multiple clinical and biochemical features is predictive of ALPL anomalies, and, therefore, they should be carefully identified. Tamoxifen emerged as a hypophosphatasemic drug.

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

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

Bone mineral density predictors in long-standing type 1 and type 2 diabetes mellitus.

BACKGROUND: Despite the increased fracture risk, bone mineral density (BMD) is variable in type 1 (T1D) and type 2 (T2D) diabetes mellitus. We aimed at comparing independent BMD predictors in T1D, T2D and control subjects, respectively. METHODS: Cross-sectional case-control study enrolling 30 T1D, 39 T2D and 69 age, sex and body mass index (BMI) - matched controls that underwent clinical examination, dual-energy X-ray absorptiometry (BMD at the lumbar spine and femoral neck) and serum determination of HbA1c and parameters of calcium and phosphate metabolism. RESULTS: T2D patients had similar BMD compared to T1D individuals (after adjusting for age, BMI and disease duration) and to matched controls, respectively. In multiple regression analysis, diabetes duration - but not HbA1c- negatively predicted femoral neck BMD in T1D (ß= -0.39, p = 0.014), while BMI was a positive predictor for lumbar spine (ß = 0.46, p = 0.006) and femoral neck BMD (ß = 0.44, p = 0.007) in T2D, besides gender influence. Age negatively predicted BMD in controls, but not in patients with diabetes. CONCLUSIONS: Long-standing diabetes and female gender particularly increase the risk for low bone mass in T1D. An increased body weight partially hinders BMD loss in T2D. The impact of age appears to be surpassed by that of other bone regulating factors in both T1D and T2D patients.

Evaluation of a Panel of MicroRNAs that Predicts Fragility Fracture Risk: A Pilot Study.

The assessment of fragility fracture risk based on bone densitometry and FRAX°, although commonly used, has shown some limitations. MicroRNAs (miRNAs) are promising biomarkers known to regulate post-transcriptional gene expression. Many studies have already shown that microRNAs are involved in bone homeostasis by modulating osteoblast and osteoclast gene expression. In this pilot study, we investigated the ability of an miRNA panel (namely, the OsteomiR° score) to predict fragility fracture risk in older people. miRNAs were extracted from the sera of 17 persons who developed a fracture within 3 years of collecting the serum and 16 persons who did not experience fractures in the same period. Nineteen miRNAs known to be involved in bone homeostasis were assessed, and 10 miRNAs were employed to calculate the OsteomiR° score. We found a trend towards higher OsteomiR° scores in individuals who experienced fractures compared to control subjects. The most suitable cut-off that maximized sensitivity and specificity was determined by ROC curve analysis, and a positive predictive value of 68% and a sensitivity of 76% were obtained. The OsteomiR° score was higher in osteopenic and osteoporotic subjects compared to subjects with a normal T score. Additionally, the OsteomiR° score predicted more fracture events than the recommended "need-to-treat" thresholds based on FRAX° 10-year probability. miRNAs reflect impairments in bone homeostasis several years before the occurrence of a fracture. The OsteomiR° score seems to be a promising miRNA panel for fragility fracture risk prediction and might have added value compared to FRAX°. Given the limited cohort size, further studies should be dedicated to validating the OsteomiR° score.

Zoledronic acid sequential therapy could avoid disadvantages due to the discontinuation of less than 3-year denosumab treatment.

INTRODUCTION: Rapid descent in bone mineral density (BMD) and ascent in bone turnover marker (BTM) occur within the short period following denosumab (Dmab) discontinuation. In addition, the incidence of vertebral fracture also rises within the short period. The purpose of this study is to investigate the effects of sequential therapy using zoledronic acid (ZOL) on any adverse events after Dmab discontinuation. MATERIALS AND METHODS: This study was a multicenter retrospective observational study, and the subjects were osteoporosis patients who visited our institutions between 2013 and 2018. We performed sequential therapy using ZOL for 30 patients who had difficulty continuing Dmab, due to physical or social reasons, and investigated the fracture incidence and BMD/BTM changes at 4 time points (at the start of Dmab, the start of ZOL, 6 months after ZOL and 12 months after ZOL). RESULTS: No new vertebral/nonvertebral fractures were observed at each time point after switching from Dmab to ZOL in any of the 30 patients. The BMD/BTM changes were evaluated in 18 of the 30 cases, since all data of lumbar/femoral neck BMDs and TRACP-5b at 4 time points was only available in 18 cases. BMDs significantly increased at each time point compared with that at the start of Dmab. Serum TRACP-5b significantly decreased at each time point compared with that at the start of Dmab. CONCLUSION: It was suggested that sequential therapy using ZOL could suppress the decrease of BMD, and increase of BTM, if the period of Dmab administration was less than 3 years.

FGF23-related hypophosphatemia in patients with low bone mineral density and fragility fractures: challenges in diagnosis and management.

PURPOSE: Hypophosphatemia (HP) can be observed in patients evaluated for skeletal fragility. We investigated prevalence of HP among outpatients referred for low bone density or fragility fractures, HP-associated clinical and biochemical features and outcomes of recommended diagnostic algorithm in our cohort. METHODS: Chronic HP (phosphate ≤ 2.7 mg/dL over 6 months or longer) was retrospectively investigated among 2319 patients. In renal wasting-related HP, intact FGF23 was assessed; non-suppressed FGF23 prompted the performance of 68Ga-DOTATOC PET/CT in the suspicion of tumor-induced steomalacia (TIO). RESULTS: Renal wasting-related HP (median 2.2, range 1.6-2.6 mg/dL) was observed in 19 patients (0.82%). FGF23 levels were suppressed in two patients diagnosed with renal tubular disease, increased in one and within normal range in most patients. X-linked hypophosphatemic rickets was diagnosed in one woman. In the remaining 16 patients, highly prevalent fragility fractures (50%) and severely reduced bone mineral density were detected, though diagnostic criteria for osteomalacia were not fulfilled. 68Ga-PET was performed in nine patients and was positive in four. While intact FGF23 levels alone failed to differentiate PET's outcomes (positive: FGF23 median 70.5 pg/mL; negative: 52 pg/mL, P = 0.462), the coexistence of multiple biochemical and radiologic alterations performed better in prediction of PET's positivity. CONCLUSION: Mild, apparently unexplained HP is observed in 0.82% of patients with low bone density or fragility fractures. In asymptomatic patients with isolated mild hypophosphatemia, the probability of finding an underlying tumor disease is very low, and utility of extensive and expensive diagnostic workup should be carefully considered in this setting.

Exon 3-deleted growth hormone receptor isoform is not related to worse bone mineral density or microarchitecture or to increased fracture risk in acromegaly.

PURPOSE: Acromegaly is a cause of secondary osteoporosis and is associated with increased risk of vertebral fractures (VFs). The influence of exon 3-deleted isoform of growth hormone receptor (d3-GHR) on bone microarchitecture has not been studied in acromegaly. AIM: The aim of this study was to analyze the associations between d3-GHR isoform and bone mineral density (BMD), bone microarchitecture, and VFs in acromegaly patients. METHODS: Consecutive acromegaly patients treated at a single reference center were included. BMD was analyzed using dual-energy X-ray absorptiometry (DXA) and bone microarchitecture was analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT). The presence of moderate to severe VFs was assessed by thoracic and lumbar X-ray. GHR genotyping was analyzed by PCR, and full-length isoform of GHR (fl-GHR) was represented by a 935-bp fragment and d3-GHR by a 532-bp fragment. RESULTS: Eighty-nine patients were included [56 females; median age at diagnosis: 43 years (17-78)]. Disease was uncontrolled in 63% of patients. At least one d3-GHR allele was present in 60% of patients. Frequency of active disease (p = 0.276) and hypogonadism (p = 1.000) was not different between patients with fl-GHR and those with at least one d3-GHR. There was no difference in any DXA or HR-pQCT parameters between patients with fl-GHR and those with d3-GHR. Significant VFs were observed in 14% of patients, but there was no difference in frequency between patients with fl-GHR and those with at least one d3-GHR allele (p = 0.578). CONCLUSIONS: Presence of d3-GHR was not associated with worse BMD or bone microarchitecture or with higher frequency of significant VFs.

Rachitic change and vitamin D status in young children with fractures.

OBJECTIVE: To examine the association between rachitic changes and vitamin D levels in children less than 2 years old with fractures. METHODS: Children less than 2 years old who were admitted to a large children's hospital for a fracture and underwent a skeletal survey were included. Two pediatric radiologists blinded to the children's vitamin D levels independently reviewed the skeletal surveys for the following rachitic findings: demineralization, widened sutures, rachitic rosary, Looser zones, and metaphyseal changes. Kappa coefficients were calculated to assess inter-rater agreement. Logistic regression was used to test the association between vitamin D level and rachitic findings. RESULTS: There were 79 subjects (40 female and 39 male) with a median age of 4 months. Vitamin D levels ranged from 11.6 to 88.9 ng/ml and were low in 27. Questionable demineralization was noted in seven subjects; mild to moderate demineralization was observed in four subjects. Widened sutures were noted in seven subjects, many also with concurrent intracranial hemorrhage. Lower vitamin D levels were associated with increased odds of demineralization after adjusting for age, gender, and prematurity (P < 0.015). An association was not found between the vitamin D level and suture widening (P = 0.07). None of the cases demonstrated Looser zones, rachitic rosary, or metaphyseal changes of rickets. CONCLUSIONS: Infants and toddlers with fractures frequently have suboptimal vitamin D levels, but radiographic evidence of rickets is uncommon in these children.

A Systematic Review and Meta-analysis of the Association Between Vitamin K Antagonist Use and Fracture.

BACKGROUND: Vitamin K antagonist (VKA) anticoagulant use is suspected to increase the risk of bone fracture through inhibition of vitamin K-dependent cofactors of bone formation, an effect not seen with non-vitamin K antagonist oral anticoagulants (NOACs). The purpose of our systematic review and meta-analysis is to investigate the association between VKA use and fracture. METHODS: We searched PubMed, EMBASE, and Cochrane Library for studies analyzing fracture in adults using VKAs versus controls. Two authors independently reviewed articles. We assessed for risk of bias using the Newcastle-Ottawa Quality Assessment Scale and the Cochrane Risk of Bias Tool and calculated pooled effects using random effects models. RESULTS: We included 23 articles (22 observational studies and 1 randomized controlled trial), studying 1,121,582 subjects. There was no increased odds of fracture in VKA users versus controls (pooled OR 1.01, 95% CI 0.89, 1.14) or in VKA users versus NOAC users (pooled OR 0.95, 95% CI 0.78, 1.15). Subjects using a VKA for 1 year or longer did not have increased odds of fracture (pooled OR 1.07, 95% CI 0.90, 1.27). Compared to controls, there was increased odds of fracture in women (pooled OR 1.11, 95% CI 1.02, 1.21) and older VKA users (≥ 65) (pooled OR 1.07, 95% CI 1.01, 1.14). DISCUSSION: We found no increase in odds of fracture in VKA users versus controls or NOAC users. There was a small increase in odds of fracture among female and elderly VKA users, which may not be clinically important when accounting for other considerations in choosing an anticoagulant. Our findings suggest that, when anticoagulation is necessary, fracture risk should not be a major consideration in choice of an agent. Future studies directly comparing VKA to NOAC users and studies with longer duration of VKA use may be needed.

Normocalcemic Primary Hyperparathyroidism in Adults Without a History of Nephrolithiasis or Fractures: A Prospective Study.

The prevalence and the diagnostic criterion of "normocalcemic" primary hyperparathyroidism (NPHPT) are still uncertain and there is no consensual definition. This prospective study evaluated the prevalence of NPHPT in 676 adults without a history of fractures or nephrolithiasis and who would be submitted to thyroidectomy, the impact of adopting different cut-off values for 25-hydroxyvitamin D and estimated glomerular filtration rate (eGFR), and the agreement between biochemical diagnosis and the surgical finding of altered parathyroid glands. NPHPT was diagnosed in patients with normal total and ionized calcium and elevated PTH (in 2 measurements) and without a known cause of secondary HPT, including eGFR<40 ml/min/1.73 m2 and 25-hydroxyvitamin D<20 ng/dl. The 4 parathyroid glands were fully explored in these patients. Forty-six patients (6.8%) had a laboratory diagnosis of NPHPT. Altered parathyroid glands were detected in only 4 patients, corresponding to 0.6% of all patients and to 8.7% of those with a biochemical diagnosis of NPHPT. The latter was confirmed in 0/174 men, 1/252 premenopausal women, and 3/250 postmenopausal women. Among the 42 patients with elevated PTH and without altered parathyroid glands, 25 had 25-hydroxyvitamin D between 20 and 30 ng/dl, 7 had eGFR between 40 and 60 ml/min/1.73 m2, and 9 had both. The prevalence of NPHPT was 0.74% in this adult population without a history of nephrolithiasis or fractures. The diagnostic criterion using eGFR>60 ml/min/1.73 m2 and 25-hydroxyvitamin D>30 ng/dl was more appropriate considering the agreement with the surgical finding of altered parathyroid glands.

Neurologic Complications of Fat Embolism Syndrome.

PURPOSE OF REVIEW: Fat embolism syndrome (FES) is a rare disorder with potentially devastating neurologic complications. This article reviews the history, pathophysiology, clinical features, diagnosis, and treatment of FES with a focus on its neurologic aspects. RECENT FINDINGS: The neurologic complications of FES are more commonly recognized with current diagnostic testing and increase awareness of the disorder. FES may present initially with neurologic manifestations. Prompt diagnosis of FES and of its neurologic manifestations could be lifesaving. This includes respiratory support and management of neurological complications. The classic clinical triad of pulmonary insufficiency, neurologic disturbances, and petechial skin rash typically presents 24 to 72 h following an initial insult, most commonly a traumatic long bone fracture. Early onset (< 24 h) and delayed onset (> 72 h) have been described. Neurologic manifestations may include ischemic/hemorrhagic strokes, retinal ischemia, seizures, autonomic dysfunction, and diffuse brain injury. Diagnosis remains clinical. Management consists mainly of supportive care.

Carboxy terminal collagen crosslinks as a prognostic risk factor for fall-related fractures in individuals with established spinal cord injury.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To study associations between specific bone turnover markers and fall-related fractures in individuals with spinal cord injury (SCI). SETTING: Rehabilitation Hospital. METHODS: Carboxy terminal collagen crosslinks (CTX), type-1 procollagen N-terminal (P1NP), albumin-corrected calcium (Ca2+), parathyroid hormone (PTH) and vitamin D were examined in a cohort of 106 participants with SCI at least 1 year post injury. The participants were followed for 1 year monitoring fall-related fractures. RESULTS: In total, 29 out of 106 reported having experienced a fall-related fracture post-injury at baseline, and 5 out of 100 had experienced a fall-related bone fracture during the 1 year follow-up. Our main findings were that high levels of serum CTX increased the odds of being in the fracture group, and that 25-hydroxy vitamin D (25 OHD) levels, Ca2+, PTH or P1NP were not associated with being in the fracture group. CONCLUSIONS: We here present an association between high-CTX plasma levels at baseline and fall-related fractures reported during a 1-year follow-up among individuals with established SCI. We recommend studies with larger SCI populations before further clinical implications can be drawn.

Factors associated with osteocalcin in men with spinal cord injury: findings from the FRASCI study.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess the association between clinical and demographic factors, bisphosphonate use, and circulating total osteocalcin levels in men with chronic spinal cord injury. SETTING: Veteran Affairs Medical Center. METHODS: As part of an epidemiological study assessing SCI-related health conditions, 214 men with chronic spinal cord injury underwent a DXA scan and provided a blood sample and information regarding SCI, medication use, and fracture history. General linear models were used to assess clinical/demographic factors of osteocalcin, and if significant, were included in multivariate model. RESULTS: We found that total osteocalcin levels increased 1.0 ng/ml for every kilogram increase in lean mass (p = 0.05) and increased 4.53 ng/ml for every ng/ml increase in C-telopeptide level (p < 0.0001). Osteocalcin levels were greater in people reporting no alcohol consumption compared with drinkers (15.49 ng/ml versus 18.58 ng/ml, p < 0.0002), lower in diabetics compared with nondiabetics (15.23 ng/ml versus 18.92 ng/ml, p = 0.0001), and lower in bisphosphonate users compared with nonusers (15.50 ng/ml versus 18.58 ng/ml, p < 0.03). The association between age and osteocalcin was not significant (p = 0.06). This model explained 58% of the variation in ln osteocalcin levels (model p < 0.0001, r2 = 0.58). CONCLUSIONS: Total osteocalcin levels vary based on health habits, body composition, comorbid illnesses, and bisphosphonate use in men with chronic spinal cord injury.

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

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

Lipid Profile and Risk of Bone Fracture: A Systematic Review and Meta-Analysis of Observational Studies.

Purpose: Earlier studies have linked lipid profile to osteoporotic fractures; however, to our knowledge, no study had summarized available data on this relationship. We aimed to summarize the current evidence on the association between lipid profile and bone fractures. Material and Methods: A systematic search of PubMed and Scopus was done to find relevant published studies until March 2018. To combine effect sizes, we applied fixed- or random-effects analysis, where appropriate. Cochran's Q test and I2 were used to assess between-study heterogeneity. Results: Overall, 11 studies (seven prospective, three cross-sectional and one case-control studies) were included in the current systematic review. Out of them, 10 studies with a total sample size of 60,484 individuals, aged 25 years or more, were used in the meta-analysis. The results showed that total cholesterol concentration was positively associated with risk of bone fracture; such that a 50-mg/dl increase in plasma level of TC was associated with 15% greater odds of bone fracture (combined effect size: 1.15, 95% CI: 1.02-1.30, P = .02). Furthermore, we found that individuals with a decreased level of HDL (<40 mg/dl) had a lower risk of bone fracture compared with those with a normal level (≥40 mg/dl) (combined effect size: 0.82, 95% CI: 0.71-0.96, P = .01). No significant association was found between plasma level of TG and LDL with the risk of bone fractures either in prospective or cross-sectional studies. Conclusions: We found that plasma levels of total cholesterol were positively associated with bone fractures. In addition, decreased levels of HDL were associated with an increased risk of osteoporotic fractures. Abbreviations: TG: triglycerides, TC: total cholesterol, HDL: high-density lipoprotein, LDL: low-density lipoprotein, OR: odds ratio, RR: relative risk, HR: hazard ratio, DXA: dual-energy X-ray absorptiometry, ICD: International Classification of Diseases, SD: standard deviation.

Serum Albumin and Future Risk of Hip, Humeral, and Wrist Fractures in Caucasian Men: New Findings from a Prospective Cohort Study.

OBJECTIVE: Low serum albumin concentration is associated with poor health outcomes, but its relationship with the risk of fractures has not been reliably quantified. We aimed to assess the prospective association of serum albumin with the risk of fractures in a general population. SUBJECTS AND METHODS: Baseline serum albumin concentrations were measured in 2,245 men aged 42-61 years in the Kuopio Is-chemic Heart Disease study. Hazard ratios (HRs) (95% confidence intervals) were calculated for incident fractures. RESULTS: A total of 121 fractures (hip, humeral, or wrist) were recorded during a median follow-up of 25.6 years. The risk of fractures increased linearly below a serum albumin concentration of ∼48 g/L. The age-adjusted HR (95% CI) for fractures per 1 standard deviation lower serum albumin was 1.24 (1.05-1.48). On further adjustment for several conventional and emerging risk factors, the HR was attenuated to 1.21 (1.01-1.45). Comparing the bottom versus top quartile of serum albumin levels, the corresponding adjusted HRs were 2.48 (1.37-4.48) and 2.26 (1.23-4.14). The association of serum albumin with fracture risk did not differ substantially according to age, body mass index, blood pressure, physical activity, alcohol consumption, socioeconomic status, inflammation, prevalent diseases, and smoking. Serum albumin at a threshold of 41.5 g/L demonstrated an area under the curve of 0.5850. CONCLUSION: In middle-aged Caucasian men, low serum albumin is associated with an increased risk of future fractures. The potential relevance of serum albumin concentrations in fracture prevention and prediction deserves further evaluation.