Prerehabilitation alanine aminotransferase blood levels and one-year mortality rates in older adults following hip fracture.

Low alanine aminotransferase (ALT) blood levels prior to rehabilitation are associated with poor function in older adults following hip fracture. We hypothesized that low ALT blood levels prior to rehabilitation were also associated with one-year mortality in this population. Included were 456 older adults (age ≥ 60 years, 82.5% women) admitted for rehabilitation following hip fracture. ALT blood levels were documented between one and six months prior to rehabilitation. Excluded were patients with ALT blood levels over 40 IU/L possibly consistent with liver injury. The main outcome was all-cause mortality one year following rehabilitation admission. The study group included 142 (31.1%) patients with low (≤10 IU/L) ALT blood levels and the control group included 314 (68.9%) patients with high-normal (11-40 IU/L) ALT blood levels. Overall, 52 (11.4%) patients died within one year following rehabilitation admission. Compared with the control group, patients with low ALT blood levels had significantly higher 1-year mortality rates [17.6 vs. 8.6%, odds ratio 2.27, 95% confidence interval (CI) 1.27-4.08]. Cox regression analysis showed that low ALT blood levels prior to rehabilitation were associated with one-year mortality (hazard ratio 1.88, 95% CI 1.08-3.28) together with age (hazard ratio 1.06, 95% CI 1.02-1.11), independent of gender. However, this association was no longer significant following adjustment also for peripheral vascular disease, admission and discharge functional independence measure scores, albumin serum levels, and length of rehabilitation. In conclusion, low ALT blood levels prior to rehabilitation are associated with one-year mortality in older adults following hip fracture. They may be used when only age and gender are known.

Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta-analysis.

BACKGROUND: Whether a causal relationship exists between milk intake and reduced risk of fractures is unclear. OBJECTIVES: We tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density (BMD). METHODS: We investigated the association between milk intake, LCT-13910 C/T (rs4988235), which is associated with lactase persistence (TT/TC) in Northern Europeans, and hip fractures in three Danish prospective studies (N = 97 811, age ≥20 years). We added meta-analyses of LCT-13910 and fractures and BMD from five published Northern European population studies. RESULTS: In the Danish studies, the adjusted hazard ratio (HR) for hip fracture per one glass per week higher milk intake was 1.00 (95% CI: 0.99-1.01). The per T-allele milk intake was 0.58 (0.49-0.68) glasses per week, but HR was 1.01 (0.94-1.09) for hip fracture. In meta-analyses of Danish studies with published Northern European population studies, the random effects odds ratio for any fracture was 0.86 (0.61-1.21; I2 = 73%) for TT vs. CC and 0.90 (0.68-1.21; I2 = 63%) for TC vs. CC. The standardized mean difference in femoral neck BMD was 0.10 (0.02-0.18; I2 = 0%) g cm-2 for TT vs. CC and 0.06 (-0.04 to 0.17; I2 = 17%) g cm-2 for TC vs. CC. There were no differences in lumbar spine or total hip BMD comparing TT or TC with CC. CONCLUSION: Genetically lifelong lactase persistence with high milk intake was not associated with hip fracture in Danish population-based cohorts. A meta-analysis combining Danish studies with published Northern European population studies also showed that lactase persistence was not associated with fracture risk. Genetic lactase persistence was associated with a higher femoral neck BMD, but not lumbar spine or total hip BMD.

Increased oxidative stress response in granulocytes from older patients with a hip fracture may account for slow regeneration.

Proximal femur fracture, a typical fracture of the elderly, is often associated with morbidity, reduced quality of life, impaired physical function and increased mortality. There exists evidence that responses of the hematopoietic microenvironment to fractures change with age. Therefore, we investigated oxidative stress markers and oxidative stress-related MAPK activation in granulocytes from the young and the elderly with and without fractured long bones. Lipid peroxidation levels were increased in the elderly controls and patients. Aged granulocytes were more sensitive towards oxidative stress induced damage than young granulocytes. This might be due to the basally increased expression of SOD-1 in the elderly, which was not further induced by fractures, as observed in young patients. This might be caused by an altered MAPK activation. In aged granulocytes basal p38 and JNK activities were increased and basal ERK1/2 activity was decreased. Following fracture, JNK activity decreased, while ERK1/2 and p38 activities increased in both age groups. Control experiments with HL60 cells revealed that the observed p38 activation depends strongly on age. Summarizing, we observed age-dependent changes in the oxidative stress response system of granulocytes after fractures, for example, altered MAPK activation and SOD-1 expression. This makes aged granulocytes vulnerable to the stress stimuli of the fracture and following surgery.

A higher serum alkaline phosphatase is associated with the incidence of hip fracture and mortality among patients receiving hemodialysis in Japan.

BACKGROUND: Monitoring of serum alkaline phosphatase (ALP) is recommended in the management of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, unlike calcium, phosphate or parathyroid hormone, the relationship between serum ALP and patient outcome receiving hemodialysis (HD) in Japan is unknown. METHODS: Baseline data of 185 277 HD patients with duration >90 days (66 ± 12 years, males 61.9%, and median HD duration of 5.8 years) were extracted from a nationwide dialysis registry at the end of 2009 in Japan. Outcomes were then evaluated using the registry at the end of 2010 using a multivariate logistic regression analysis. RESULTS: During 1-year follow-up, 14 230 (7.9%) patients died of all causes, including 6396 (3.6%) cardiovascular deaths. In addition, 1586 patients (1.0%) were newly diagnosed as hip fractures. All-cause and cardiovascular mortality and the incidence of hip fracture were higher in line with the increase in baseline serum ALP. On multivariate analysis, patients with the highest ALP quartile had higher all-cause and cardiovascular mortalities and a higher incidence of hip fracture than those with the lowest quartile [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.33-1.60; OR 1.25, 95% CI 1.10-1.42; and OR 1.71, 95% CI 1.33-2.18, respectively]. CONCLUSIONS: In this large cohort study, higher serum ALP levels were independently associated not only with mortality but also with the incidence of hip fracture in Japanese HD patients. Further study is needed to test whether serum ALP measurements could improve the patient outcomes.

[Methylenetetrahydrofolate reductase polymorphism C677T in patients with consolidated fractures and pseudarthrosis of long bones: relationship with homocystein and inflammatory mediators].

In article described research the results of the prevalence of the genetic polymorphism of the gene Methylentetrahydrofolatereductase C677T (MTHFR) in 130 patients with pseudarthrosis of long bones and in those with consolidated fractures. The incidence of allele-T among patients with pseudarthrosis was 1.4 times higher than among those with consolidated fractures. Pathological genotype MTHFR 677-TT was associated with the development avital types of pseudarthrosis and increase the proportion of people with hyperhomocysteinemia, high content of inflammatory mediators and development refracture.

Plasma homocysteine, folate, and vitamin B 12 and the risk of hip fracture: the hordaland homocysteine study.

UNLABELLED: Homocysteine and related factors were evaluated as risk factors for subsequent hip fractures among 4766 elderly men and women. High levels of homocysteine and low levels of folate predicted fracture, whereas vitamin B12 and genotypes were not related to fracture risk. High homocysteine may be a modifiable risk factor for hip fracture. INTRODUCTION: Elevated plasma total homocysteine (tHcy) and deficiencies of folate and vitamin B12 are associated with risk of osteoporosis and fracture. We examined whether plasma levels of tHcy, folate, and vitamin B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298C-->T polymorphisms predicted hip fracture. MATERIALS AND METHODS: This was a population-based prospective study of 2639 women and 2127 men who were 65-67 yr at enrollment in 1992-1993. Information on hip fracture was obtained from computerized records of discharge diagnoses from all hospitalizations in the region in the period between enrollment and November 30, 2005. Cox proportional hazard regression was used to estimate fracture risk according to levels of plasma tHcy, folate, and vitamin B12 and for different genotypes. RESULTS: Over a median follow-up period of 12.6 yr, hip fracture was recorded in 184 (7.0%) women and 90 (4.2%) men. The adjusted hazard ratio (95% CI) for fracture in subjects with high (>or=15 microM) compared with low levels (<9.0 microM) of tHcy was 2.42 (1.43-4.09) among women and 1.37 (0.63-2.98) among men. Dose-response analyses indicated a positive association between plasma tHcy and risk of fracture in both sexes and a negative association between plasma folate and risk of fracture among women only. Plasma vitamin B12 level or MTHFR genotype was not significantly related to risk of fracture after adjustments for confounding factors. The association between tHcy and risk of hip fracture was only slightly weakened by adjustments for plasma levels of vitamin B12 and folate. CONCLUSIONS: tHcy seems to be a predictor for hip fracture among elderly men and women. Folate was a predictor among women only, whereas vitamin B12 and MTHFR genotype did not predict hip fracture. Our data corroborate the hypothesis that homocysteine may play a role in the pathogenesis of osteoporotic fractures.

Increased collagen degradation around loosened total hip replacement implants.

OBJECTIVE: To assess collagen degradation and its relationship to some of the key collagenolytic proteinases in the aggressive synovial membrane-like interface tissue around aseptically loosened hip replacement implants. METHODS: The medical indication for the primary total hip replacement was osteoarthritis in all study patients. Samples from the study patients were compared with control synovial membranes obtained from trauma (hip fracture) patients. Proteoglycans were extracted with 4M guanidinium chloride. Denatured collagen in the remaining matrix was solubilized with alpha-chymotrypsin. Nonsoluble matrix and supernatant fractions were acid hydrolyzed before measurement of hydroxyproline. The proportion of soluble (in vivo-degraded) collagen of the total sample collagen content was calculated. Proteinases were stained using the avidin-biotin-peroxidase complex method. RESULTS: Collagen in the interface membrane from the implants was highly degraded (mean +/- SEM 20 +/- 3%) compared with that in the control synovial membranes (12 +/- 1%; P = 0.007). In controls, the degree of collagen degradation did not correlate with levels of matrix metalloproteinase 1 (MMP-1), MMP-13, or cathepsin K, although MMP-1 approached statistical significance. In interface membranes, the correlations were r = 0.88 (P = 0.002), r = 0.92 (P = 0.001), and r = 0.98 (P < 0.0001) for MMP-1, MMP-13, and cathepsin K, respectively. CONCLUSION: In normal synovial membrane, collagen matrix remodeling may be mainly an intracellular process. In contrast, pathologic tissue destruction in the interface membrane from prosthetic hip joints is associated with a shift toward MMP-13 and cathepsin K, which become activated and overcome their endogenous inhibitors (tissue inhibitors of metalloproteinases and cystatin C). The highly significant correlation between collagen degradation and cathepsin K indicates an extracellular role of this acidic endoproteinase, consistent with previous observations concerning the acidity of the interface membrane.

Association of a common allelic polymorphism (C677T) in the methylene tetrahydrofolate reductase gene with a reduced risk of osteoporotic fractures. A case control study in Danish postmenopausal women.

Twin studies indicate a substantial genetic component in the development of osteoporosis. One of the latest studied candidate genes is the one coding for methylene tetrahydrofolate reductase (MTHFR) (C677T) in which a point mutation gives rise to a thermolabile variant of MTHFR. The aim of this study was to investigate the influence of this mutation on peripheral measures of bone density and on the odds ratios (OR) for hip and lower forearm fracture in a case control study of Danish postmenopausal women. A total of 74 women with lower forearm fracture, 41 women with hip fracture, and 207 age-matched controls were included. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel as well as bone mineral density (BMD) measured by dual X-ray absorptiometry at the distal forearm. The MTHFR (C677T) genotypes were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Only 2 of 21 individuals with the TT genotype had sustained a fracture as opposed to 46 of 142 with the CT genotype and 67 of 159 with the CC genotype (P = 0.007). Using logistic regression, the following odds ratios were found when comparing the individuals homozygotic for the C-allele with those homozygotic for the T-allele: lower forearm fracture OR = 3.93 (1.25; 12.40, P = 0.02), hip fracture OR = 6.99 (l.35; 36.92, P = 0.02) and the fractures combined OR = 4.33 (1.73; 10.81, P = 0.002). In this study, the MTHFR (C677T) genotypes were not significantly associated with BMD at the lower forearm or with ultrasound parameters measured at the calcaneus. However, a significant increase in the odds ratio of fracture was found for the wild-type C-allele.

Comparison of bone and total alkaline phosphatase activity on bone turnover during menopause and in patients with established osteoporosis.

OBJECTIVE: Recently, a bone alkaline phosphatase (AP) enzyme immunoassay (EIA) was developed for measurement of bone AP activity with a monoclonal antibody. We compared the clinical performance of bone AP (bAP) measured by EIA and total AP (tAP) to examine if bAP is preferable to tAP as a bone formation marker in the post-menopause and established osteoporosis. DESIGN AND PATIENTS: Serum was obtained from 50 pre- and 93 post-menopausal healthy women, and 54 osteoporotic patients with vertebral fractures and 57 patients with hip fracture. MEASUREMENTS: Total AP was measured spectrophotometrically with p-nitrophenyl phosphate as substrate. The intra- and inter-assay coefficients of variation were 0.7-1.8% and 0.6-1.1%, respectively. Bone AP activity (bAP) was measured by EIA kit, ALKPHASE-B (Metra Biosystems, Inc.) using a monoclonal antibody against human bone AP. The intra- and inter-assay CVs were 4.0-8.3% and 6.2-7.9%, respectively. RESULTS: The percentage mean increase of bAP (54.9%) in post-menopausal subjects over premenopausal subjects was higher than that of tAP (40.1%). In age-matched comparison, % mean increases were 57.5% for bAP and 35.3% for tAP. Z-score for bAP in post-menopausal subjects was significantly higher than that for tAP. However, there was no significant difference in Z-scores between tAP and bAP in osteoporotic patients with vertebral fractures or with hip fracture. The correlation coefficient of bAP with age (r = 0.316) was similar to that of tAP with age (r = 0.319). In post-menopausal subjects, there was no difference in the concentrations of tAP nor bAP among the groups in whom times since the menopause was 0-9 years, 10-19 years and more than 20 years. Bone AP was highly correlated to tAP in the normal subjects, the patients and the total study group. CONCLUSION: Preference can be given to bone AP by enzymatic immunoassay over total AP based on their clinical utility during the menopause; however, no preference can be given to bone AP over total AP in established osteoporosis.

Perioperative creatine phosphokinase trends in elderly patients with hip fracture.

A prospective study of the serum levels of unfractionated creatine phosphokinase (CPK) in 69 consecutive elderly patients undergoing surgery for hip fracture is reported. Serum unfractionated CPK levels were measured on admission, on the evening following surgery and daily for the first five days post-operatively. All of the CPK levels measured on admission were within the normal range for this laboratory. A gradual rise in CPK levels followed surgery. On the evening following surgery 75% of values were greater than the upper limit of the normal reference range. The peak values were seen on day 1 post-operatively but 25% of values were still less than the reference maximum. A gradual decline was seen after this and at day 5 post operatively 50% of values were within the normal reference range. A single unfractionated CPK determination is not of diagnostic benefit in the post-operative period in elderly patients with hip fracture. However, patients with intracapsular and intertrochanteric fractures do not show elevation of unfractionated CPK levels prior to surgery.

Operative treatment of acute hip fractures: its effect on serum creatine kinase, lactate dehydrogenase and their isoenzymes.

Serum creatine kinase, lactate dehydrogenase, and their isoenzymes were prospectively studied in 16 patients who underwent operative treatment of acute hip fractures. No perioperative myocardial infarctions occurred; however, two patients died of noncardiac causes. We found that skeletal muscle injury associated with operative treatment of acute hip fractures did not result in significant elevations of serum CK-MB or the LD-1/LD-2 ratio. CK-MB activity exceeding 5% of total CK activity was observed in five patients who did not experience acute perioperative myocardial infarction; however, no patient had an absolute CK-MB value exceeding 50 IU/L. Elevations of serum CK-MB exceeding 50 IU/L and a LD-1/LD-2 ratio exceeding 1.0, therefore, should not be attributed to skeletal muscle injury alone following the operative treatment of acute hip fractures.

Vitamin D concentrations in women of postmenopausal age with fractures of the femoral neck.

Thirty-eight women of postmenopausal age, suffering from fractures of the femoral neck or vertebral bodies were studied in relation to differences in bone metabolism. The blood and urinary changes concerned in mineral and bone metabolism were recorded within 10 days of trauma, and in some femoral neck fractures, a histological study of the femoral heads removed in the course of prosthetic substitution was carried out. The patients with femoral neck fractures were older than those with vertebral fractures and had metabolic and histological findings suggestive of osteomalacia. A particularly significant difference between the two groups was the plasma level of 25 hydroxycholecalciferol, which was lower in femoral neck fractures, and the urinary excretion of calcium, which was also more reduced in femoral neck fractures. A deficit of vitamin D hepatic metabolite thus appears to be a risk factor for femoral neck fractures in old patients.

Changes in serum alkaline phosphatase after femoral fractures.

Osteomalacia may be a contributory factor in some patients in the development of fractures of the femoral neck and complicate the subsequent management. The level of serum alkaline phosphatase is often valuable in the diagnosis of metabolic bone disease but rises after any uncomplicated fracture, and since such a rise may limit the diagnostic usefulness of this measurement in detecting osteomalacia its extent was assessed in 106 patients. In the majority serum levels were normal on admission, rising after seven to nine days to reach a maximum within a month after fracture. Elevated levels on admission were found in patients with osteomalacia, liver damage or where there had been a delay of several weeks between injury and admission. In a small number of patients normal levels on admission subsequently reached very high values, usually in association with comminution or instability of the fracture. Elevated levels persisted for six to twelve weeks after fracture, the major influence upon the level at this time being the maximum value achieved rather than the presence of osteomalacia. If patients are to be screened for osteomalacia, the alkaline phosphatase must be measured within the first week after a fracture to avoid the distorting influences of the fracture itself.