Intertrochanteric Region Research Articles

Stability of Bone Density and Bone Quality Measures in Special Warfare High Speed Craft Operators

Special Warfare Combatant-craft Crewmen (SWCC) are subjected to frequent and intense mechanical shock as a part of their duties. In addition, they partake in a very rigorous physical conditioning program that includes resistance training, core development training, and running and swimming. It is unclear what, if any, changes might be expected in bone density and quality parameters over the course of a career of high-intensity exercise and frequent mechanical shock exposure. PURPOSE: The purpose of this study was to carry out a comparison of bone density and bone quality measures of SWCC who had different years of boat service (BOATIME). METHODS: Dual-energy X-ray absorptiometry (DXA) measurements were made on 59 SWCC (age 28.5 ± 5.6 y; stature 177.8 ± 7.3 cm; weight 87.2 ± 13.1 kg, % fat 17.7 ± 4.8) and 57 Students who just completed SWCC training and were about to enter boat service (age 22.4 ± 3.3 y; stature 177.3 ± 4.3 cm; weight 78.3 ± 7.7 kg, % fat 14.5 ± 2.3), and who represented the entry conditions. A whole-body scan and a hip scan were performed. Whole-body (WB), lower-limb (LL) and upper-limb (UL) bone mineral density (BMD) measures were obtained from the whole-body scan. The hip scan was used to provide a Hip Structural Analysis (HSA; Beck, 1990). The HSA provided estimates of cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), and strength modulus (MOD), for the narrow-neck (NN), inter-trochanteric region (IT), and upper shaft (S) of the femur. RESULTS: Mean BOATIME for the SWCC was 3.3yrs with a range of 2 mos to 14.75 yr. BOATIME for the students was 0 mos. Mean values for the entire sample (SWCC and students) were ULBMD, 0.964 ± 0.810; LLBMD, 1.472 ± 0.137; WBBMD, 1.336 ± 0.118; ITCSA, 7.09 ± 1.20; ITC SMI, 21.60 ± 5.78; ITMOD, 6.52 ± 5.78; NNCSA, 4.13 ± 0.63; NNCSMI, 3.91 ± 0.89; NNMOD, 2.19± 0.41; SCSA, 5.82± 0.77; SCSMI, 4.94 ± 1.15 and SMOD, 3.16 ± 0.55. Mean values did not differ between SWCC and students. No significant associations with BOATIME were found for any of the variables. CONCLUSION: Bone density and bone quality values appear to remain unchanged for SWCC throughout their careers.

Treatment with Zoledronic Acid Ameliorates Negative Geometric Changes in the Proximal Femur following Acute Spinal Cord Injury

Acute spinal cord injury is associated with rapid bone loss and an increased risk of fracture. In this double-blind, randomized, placebo-controlled trial, 17 patients were followed for 1 year after administration of either 4 or 5 mg of zoledronic acid or placebo. Bone mineral density (BMD) and structural analyses of the proximal femur were performed using the hip structural analysis program at entry, 6 months, and 12 months. The 17 subjects completed 12 months of observation, nine receiving placebo and eight zoledronic acid. The placebo group showed a decrease in BMD, cross-sectional area, and section modulus and an increase in buckling ratio at each proximal femur site at 6 and 12 months. Six months after zoledronic acid, BMD, cross-sectional area, and section modulus increased at the femoral neck and intertrochanteric regions and buckling ratio decreased consistent with improved bone stability. However, at 12 months, the femoral narrow-neck values declined to baseline. In contrast to placebo, the intertrochanteric region and femur shaft were maintained at or near baseline through 12 months in the zoledronic acid-treated group. Urine N-telopeptide excretion was increased at baseline and declined in both the placebo and treatment groups during the 12 months of observation. We conclude that a single administration of zoledronic acid will ameliorate bone loss and maintain parameters of bone strength at the three proximal femur sites for 6 months and at the femur intertrochanteric and shaft sites for 12 months.

Alterations in Proximal Femur Geometry in Children Treated with Glucocorticoids for Crohn Disease or Nephrotic Syndrome: Impact of the Underlying Disease

Proximal femur geometry was assessed in children and young adults treated with chronic GCs for CD or SSNS. Subperiosteal width and section modulus were significantly lower in CD and greater in SSNS compared with controls, highlighting the importance of the underlying disease, persistent inflammation, and alterations in lean mass. The impact of glucocorticoid (GC) therapy on bone structure during growth is unknown. Our objective was to characterize proximal femur geometry in children and young adults with Crohn disease (CD) or steroid-sensitive nephrotic syndrome (SSNS) compared with controls and to evaluate the influence of lean mass and GC therapy on bone parameters. DXA scans of the hip and whole body were obtained in 88 subjects with CD, 65 subjects with SSNS, and 128 controls (4-26 years of age). Hip structural analysis parameters (subperiosteal width, cross-sectional area [CSA], and section modulus in the narrow neck [NN], intertrochanteric region [IT], and femoral shaft [FS]), areal BMD, and whole body lean mass were expressed as Z scores compared with controls. Multivariable linear regression was used to adjust outcomes for group differences in age, sex, race, and height. Mean lean mass Z scores were lower in CD (-0.63, p < 0.001) and greater in SSNS (0.36, p = 0.03) compared with controls. Hip areal BMD Z scores were lower in CD (-0.73, p < 0.001) but not SSNS (-0.02, p > 0.2) compared with controls. In CD, Z scores for subperiosteal width (NN: -1.66, p < 0.001; FS: -0.86, p < 0.001) and section modulus (NN: -0.60, p = 0.003; FS: -0.36, p = 0.03) were significantly lower than controls. In contrast, in SSNS, Z scores were greater for IT subperiosteal width (0.39, p = 0.02), FS CSA (0.47, p = 0.005), and FS section modulus (0.49, p = 0.004). Alterations in section modulus in CD and SSNS were eliminated after adjustment for lean mass. Cumulative GC dose was inversely associated with FS subperiosteal width and section modulus only in CD. These data show that the effects of GC on proximal femur geometry during growth are influenced by the underlying disease, persistent inflammation, and alterations in lean mass. These data also provide insight into the structural basis of hip fragility in CD.

Predicting Failure Load of the Femur with Simulated Osteolytic Defects using Noninvasive Imaging Technique in a Simplified Load Case

Currently, there is no proven sensitive or specific method for predicting pathological fracture of the femur. The clinical management of lytic femoral metastases is based on geometric measurement of the bone, of the defect, or both. However, the mechanical behavior of a structure depends on both its material and geometric properties. Our hypothesis is that a change in bone structural properties as the result of tumor induced osteolysis determines the fracture risk in bones with skeletal metastases. We developed a method of QCT (Quantitative Computed Tomography) combined with engineering beam analysis as a noninvasive tool for measuring the material and geometric properties of the femur with simulated lytic defects in the intertrochanteric region. In this ex-vivo study we prove that engineering beam structural analysis applied to serial transaxial QCT scans through human femora with simulated lytic defects at the proximal femur predicts the load at failure and location of fracture better than current clinical guidelines. Structural rigidity measured by QCT in this study may be used to predict the load carrying capacity of femurs with metastatic defects and, furthermore, may be used when the tumor has weakened the bone sufficiently such that pathological fracture is imminent and prophylactic stabilization is necessary.

Multiple primary tumors associated with chromosome 9p deletion

Multiple primary tumors associated with chromosome 9p deletion

Noninvasive Imaging Technique Predicts Failure Load of the Femur with Simulated Osteolytic Defects

Objective. To determine whether the load-carrying capacity of human proximal femora with simulated lytic defects can be predicted using QCT-derived simplified beam theory. Design. The predicted fracture load of simulated defects were calculated using new technique of QCT combined with engineering beam analysis. Patients. Simulated lytic defects were created using a surgical drill in the intertrochanteric region of twenty human cadaveric femora. QCT scans were conducted before and after creating defects on either AM (Anterior-Medial) or PL (Posterior-Lateral) regions. Results. A linear relation could be used to predict failure load from the proposed engineering analysis based on QCT scan. The coefficient of determination analysis of QCT-derived predicted load vs. the measured failure load was R2=0.73 (p&lt;0.0001). Conclusions. The data suggest that three quarters of human femoral failure can be predicted in vivo, i.e. using QCT scan. Combined with information on the loads associated with the activities of daily living, these data may be used to prevent pathologic fractures of patients who had prior surgery of removing tumors on proximal femurs.

THE CLASSIC: Metal Hip Joint

THE CLASSIC: Metal Hip Joint

Interlimb Differences in Lower Extremity Bone Mineral Density Following Anterior Cruciate Ligament Reconstruction

Prospective descriptive study. To determine the extent of bone mineral density (BMD) interlimb differences at several hip locations in the involved versus noninvolved lower extremity following anterior cruciate ligament (ACL) surgery. Disuse following ACL reconstruction can be extensive. This disuse not only affects the soft tissue, but may also affect the skeletal structure. The extent of this disuse specific to the proximal femur has not been previously determined. BMD was assessed in 15 subjects, 17 to 51 years old, who were between 6 and 32 months post-ACL reconstruction surgery. Bone mineral content (BMC) and BMD of the femoral neck, trochanteric region, intertrochanteric region, and entire hip were measured as a primary emphasis of this study. BMD and BMC of the entire lower extremities were also measured bilaterally. BMD was significantly less in the involved lower extremity compared to noninvolved lower extremity at several hip sites: 6.6% less (P<.001) for the trochanteric region, 4.0% less (P<.001) for the entire hip, and 3.4% less (P = .004) for the intertrochanteric region. No significant differences were noted comparing the entire lower extremities for either BMD (0.9%, P = .48) or BMC (3.7%, P= .09). BMD differences at the hip are significant in patient's postoperative ACL reconstruction, especially in the trochanteric region.

PR_126: Recurrent Idiopathic Transient Osteoporosis of the Hip Affecting the Contralateral Hip: A Case Report

Setting: Outpatient physical medicine and rehabilitation clinic. Patient: A 50-year-old active man referred from an orthopedic clinic with a 1-month history of progressive right hip pain. Case Description: The patient denied any trauma or preceding injury. Pain progressed to a disabling stage, with difficulty ambulating. Pain was exacerbated by weight bearing and hip rotation, and relieved with rest. Magnetic resonance imaging (MRI) revealed diffuse homogenous bone marrow edema with decreased signal intensity on T1 images and increased signal intensity on T2 images involving the right femoral head and neck into the intertrochanteric region.

Proximal hip geometry is linked to several chromosomal regions: Genome-wide linkage results from the Framingham Osteoporosis Study

Introduction Femoral geometry contributes to bone strength and predicts hip fracture risk. The purpose of this study was to evaluate heritability ( h 2) of geometric indices of the proximal hip and to perform whole-genome linkage analyses of these traits, adjusted for body size. Methods DXA scans of the proximal femur from 1473 members of 323 pedigrees (age range 31–96 years) from the population-based Framingham Osteoporosis Study were obtained. Using the hip structural analysis program, we measured femoral neck length (FNL, cm) and neck-shaft angle (NSA); subperiosteal width (WID, cm), cross-sectional area (CSA, cm 2); and section modulus (Z, cm 3) at the narrowest section of the neck (NN), intertrochanteric (IT) and femoral shaft (S) regions. Linkage analyses were performed for the above indices with a set of 636 markers using variance components maximum likelihood method. Results Substantial genetic influences were found for all geometric phenotypes, with h 2 values between 0.28 (NSA) and 0.70 (IT_WID). Adjustment for height and BMI did not alter h 2 of NSA and FNL but decreased h 2 of the cross-sectional indices. We obtained substantial linkage (multipoint LOD > 3.0) for S_Z at 2p21 and 21q11 and S_WID at Xq25–q26. Inclusion of height and BMI as covariates resulted in much lower LOD scores for S_Z, whereas linkage signals for S_Z at 4q25, S_CSA at 4q32 and S_CSA and S_Z at 15q21 increased after the adjustment. Linkage of FNL at 1q and 13q, NSA at 2q and NN_WID at 16q did not change after the adjustment. Conclusion Suggestive linkages of bone geometric indices were found at 1q, 2p, 4q, 13q, 15q and Xq. The identification of significant linkage regions after adjustment for BMI and height may point to QTLs influencing femoral bone geometry independent of body size.

Contribution of Three-Dimensional Trabecular Bone Microstructure of the Proximal Femur to its Mechanical Properties as Assessed by Micro-Finite Element Analysis

The purpose of this study was to investigate the contribution of the microstructural properties of trabecular bone in predicting its elastic modulus in the intertrochanteric region. A total of 15 trabecular bone core specimens were obtained from the proximal femurs of patients undergoing total hip arthroplasty. The micro-computed tomography (micro-CT) was used to scan each specimen to obtain micro-morphology. Microstructural parameters were directly calculated using software. Micro-CT images were converted to micro-finite element model using meshing technique, and then micro-finite element analysis (FEA) was performed to assess the mechanical property (Young’s modulus) of trabecular bone. The results showed that the ability to explain this variance of Young’s modulus is improved by combining the structural indices with each other. It suggested that assessment of bone microarchitecture should be added as regards detection of osteoporosis and evaluation of the efficacy of drug treatments for osteoporosis.

The Human Calcium-Sensing Receptor and Interleukin-6 Genes are Associated with Bone Mineral Density in Chinese

Calcium sensing receptor (CASR) is a central factor involved in calcium metabolism. Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in osteoclast differentiation. Thus, both CASR and IL-6 are important in bone and mineral metabolism and are prominent candidate genes for osteoporosis. The study aimed to test association and/or linkage between the CASR and IL-6 genes with bone mineral density (BMD) variation in a Chinese population. A cytosine-adenine ( CA) n repeat polymorphism in the CASR gene and the IL-6 gene was genotyped, respectively, in 1 263 subjects from 402 Chinese nuclear families. Employing tests implemented in the program QTDT (quantitative transmission disequilibrium tests), a significant total association of the CASR (CA) 12 allele ( P = 0.006) and (CA) 18 allele ( P = 0.02) with BMD at the femoral neck was found. For the IL-6 gene, significant within-family associations were found between the ( CA) 14 allele and BMD at the total hip ( P = 0.021), the femoral neck ( P = 0.041), and the intertrochanteric region ( P = 0.029). A significant linkage was also observed between IL-6 CA repeat polymorphism and BMD at the spine ( P = 0.001). The results suggest that the CASR gene and the IL-6 gene may have effects on BMD variation in Chinese.

Structural and remodeling indices in the cancellous bone of the proximal femur across adulthood

Fragility fractures, including fractures of the femoral neck, result from reductions in the amount, quality and architecture of bone. However, investigations of the underlying structural changes that might predispose to fracture have been largely limited to skeletal sites that do not fracture, such as the iliac crest (IC). The aim of this study was to use histomorphometry to map changes in the architecture and the static remodeling indices of cancellous bone, as a function of age and sex, in bone samples taken from the intertrochanteric (IT) region of the proximal femur at routine autopsy (18–88 years of age). Bone samples for histology were processed from 10-mm cubes of IT cancellous bone. Histomorphometry was performed using an ocular-mounted 10 × 10 graticule at a magnification of × 100. An age-dependent decrease in trabecular bone volume was observed in both females and males, as expected ( r = − 0.75 and r = − 0.63, p < 0.001, respectively). The underlying mechanisms for bone turnover appeared to be different between males and females. Thus, while the static index of bone resorption (ES/BV) was positively age-dependent in males and females ( p < 0.001, p < 0.03, respectively), the index of bone formation (OS/BV) correlated positively with age in the female group only ( p < 0.001 vs. NS). Perhaps reflecting an increase in bone formation in older females, the OS/ES ratio was greater in older females than younger females or males. Surprisingly, while resorption indices increased in older males compared with their younger counterparts, bone formation indices increased only in the older female cohort. The IT region in the proximal femur is adjacent to the site commonly involved in fragility fracture. With the limitation that these results describe cross-sectional data, they provide useful insights into changes in the cancellous bone structure and at the bone surface of females and males over the age range of 20–90 years, at a clinically relevant skeletal site.

Evidence for reduced bone formation surface relative to bone resorption surface in female femoral fragility fracture patients

Fragility fractures, including neck of femur fractures, result from reductions in the amount, quality and architecture of bone. The aim of this study was to compare the cancellous bone structure, and static indices of bone turnover, in female patients, who had sustained fragility fracture at the femoral neck, with age-matched females without fragility fracture. Bone samples were taken from the intertrochanteric region of the proximal femur of female patients undergoing hip arthroplasty surgery for a subcapital fragility fracture of the femoral neck (#NOF) or from age-matched female control individuals at routine autopsy. Contiguous bone samples were analyzed for undecalcified histomorphometry and for mRNA expression. The histomorphometric data, which were normally distributed, indicated no difference between the mean values for any of the structural parameters in control and fracture samples. In particular, the bone volume (BV/TV) values were not different and did not change significantly with age in these cohorts of individuals aged >65 years. The static indices of bone turnover, eroded surface (ES/BS) and osteoid surface (OS/BS), were positively correlated with age in the >65-year-old control group (p<0.055 and p<0.03, respectively). The median values for these indices were not different between the fracture and control groups. However, both the median and the range of OS/BS values were increased for >65-year-old controls compared with a group of younger females aged <65 years, suggesting an increase in bone formation surface in older females in the proximal femur after 65 years of age. When the data were further interrogated, a reduction in the percentage osteoid surface to eroded surface quotient (OS/ES) was found for the fracture group compared with the age-matched control group suggesting a reduced adaptive modeling drift capability in the fracture group. In contiguous bone samples, increased median values for receptor activator of nuclear factor kappa β (RANK) and interleukin-6 (IL-6) mRNA expression were observed in the fracture group. Study of cultured human osteoblasts showed that recombinant human IL-6 (rhIL-6) inhibited osteoblast differentiation, as measured by an increase in the immature osteoblast marker, STRO-1 and concomitantly decreased expression of the osteoblast maturation marker, alkaline phosphatase. Importantly, cells cultured in the presence of IL-6 showed significantly less mineral deposition in vitro compared with control cultures. These data suggest that perturbations in bone formation surface, relative to resorption surface, are potentially important in producing bone in the proximal femur with increased propensity to fracture.

Structural effects of raloxifene on the proximal femur: results from the multiple outcomes of raloxifene evaluation trial

Raloxifene improves spine bone mineral density (BMD), and its ability to reduce vertebral fractures by 40-50% suggests that it increases vertebral strength. Positive effects on hip BMD suggest a similar strengthening of the hip, but dimensional ambiguities in BMD by dual energy x-ray absorptiometry (DXA) make it difficult to infer strength effects directly. Hip fractures may be too infrequent to evaluate in practical clinical trials; even the Multiple Outcomes of Raloxifene Evaluation (MORE) study with 7,705 subjects was insufficiently powered to show a comparable reduction in hip fractures. An alternative evaluation of hip DXA data in structural terms should provide more direct evidence of treatment effects on hip strength. Hip scans from a subset of the MORE study, including 4,806 postmenopausal women with osteoporosis randomized to daily oral doses of placebo, 60 mg, or 120 mg of raloxifene were reanalyzed by the hip structure analysis (HSA) method. Scans acquired at baseline, 1, 2, and 3 years were evaluated to extract BMD and cross-sectional geometry across the narrowest point on the neck (NN), the intertrochanteric region (IT), and the proximal shaft 1.5 times the minimum neck width distal to the intersection of the neck and shaft axes. While femur outer diameter expanded during follow-up at all three regions, there were no differences in expansion between groups; treatment influenced mainly the amount and distribution of bone within cross-sections. Effects were similar at the two dose levels at the NN region although the 120 mg dose produced a greater effect on section modulus (SM) at the IT region and on BMD, bone cross-sectional area (CSA), SM, average cortical thickness (CT), and buckling ratio (BR) at the shaft region. Compared with placebo after 3 years, treatment groups showed 0.4-2% higher BMD, CSA, SM, and CT and 1-2% lower BR. The smallest treatment effects were evident at the shaft at 60 mg. We conclude that raloxifene does not influence periosteal apposition in the proximal femur but it nevertheless produces small but significant improvement in resistance to axial and bending stresses (CSA and SM, respectively) at all analyzed regions. The significant reductions in buckling ratio suggest that additional strength loss due to cortical instability is also ameliorated by treatment.

Differential gene expression of bone anabolic factors and trabecular bone architectural changes in the proximal femoral shaft of primary hip osteoarthritis patients

Previous studies have shown a generalised increase in bone mass in patients with osteoarthritis (OA). Using molecular histomorphometry, this study examined the in vivo expression of mRNA encoding bone anabolic factors and collagen type I genes (COL1A1, COL1A2) in human OA and non-OA bone. Bone samples were obtained from the intertrochanteric (IT) region of the proximal femur, a skeletal site distal to the active site of disease, from individuals with hip OA at joint replacement surgery and from autopsy controls. Semi-quantitative reverse transcription-polymerase chain reaction analysis revealed elevated mRNA expression levels of alkaline phosphatase (p < 0.002), osteocalcin (OCN) (p < 0.0001), osteopontin (p < 0.05), COL1A1 (p < 0.0001), and COL1A2 (p < 0.002) in OA bone compared to control, suggesting possible increases in osteoblastic biosynthetic activity and/or bone turnover at the IT region in OA. Interestingly, the ratio of COL1A1/COL1A2 mRNA was almost twofold greater in OA bone compared to control (p < 0.001), suggesting the potential presence of collagen type I homotrimer at the distal site. Insulin-like growth factor (IGF)-I, IGF-II, and transforming growth factor-β1 mRNA levels were similar between OA and control bone. Bone histomorphometric analysis indicated that OA IT bone had increased surface density of bone (p < 0.0003), increased trabecular number (Tb.N) (p < 0.0003), and decreased trabecular separation (Tb.Sp) (p < 0.0001) compared to control bone. When the molecular and histomorphometric data were plotted, positive associations were observed in the controls for OCN/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) versus bone tissue volume (r = 0.82, p < 0.0007) and OCN/GAPDH versus Tb.N (r = 0.56, p < 0.05) and a negative association was observed for OCN/GAPDH versus Tb.Sp (r = -0.64, p < 0.02). These relationships were not evident in trabecular bone from patients with OA, suggesting that bone regulatory processes leading to particular trabecular structures may be altered in this disease. The finding of differential gene expression, as well as architectural changes and differences in molecular histomorphometric associations between OA and controls, at a skeletal site distal to the active site of joint degeneration supports the concept of generalised involvement of bone in the pathogenesis of OA.

Effect of Alcoholon the Expression of VEGF-A,PEDF,and VEGFR-2 of Osteoblast in Avascular Necrosis of Femoral Head

Purpose : The aim of this study was to determine the effect of alcohol on the expression of VEGF-A, PEDF, and VEGFR-2 in human osteoblasts. Materials and Methods : Human osteoblasts primarily derived from the intertrochanteric region of the femur with osteonecrosis and fracture (control) were cultured with alcohol (0, 20, 100, 150 mM). The level of cell proliferation and the expression levels of VEGF-A mRNA, PEDF mRNA, and VEGFR-2 mRNA was evaluated according to the alcohol concentrations and the culture periods. Results : Osteoblasts with the added alcohol showed an early increase in cell population, and a subsequent decrease or steady level thereafter compared with those without alcohol (p＜0.05). The osteoblasts in the osteonecrosis group showed an increase in VEGF-A mRNA and PEDF mRNA expression at high alcohol concentrations (100, 150 mM), resulting in an decreased VEGF-A/PEDF ratio, while those in the control group showed an increase in VEGF-A mRNA expression and a decrease in PEDF mRNA expression, resulting in an increase in the VEGF-A/PEDF ratio (p＜0.05). Conclusion : Alcohol stops the proliferation of osteoblasts and can cause an imbalance between VEGF-A and PEDF, thereby inhibiting the neovascularization of osteonecrosis.

Clinical Evaluation of Bone Mineral Density (BMD) and Bone Metabolism in Hereditary Hemochromatosis (HH).

Background: Skeletal complications of HH have been reported, to include osteopenia and osteoporosis. However, systematic assessments of bone density and bone metabolism in healthy HH subjects have not been performed, nor have such results been compared prospectively with an appropriate control group.Methods: Thirty-five C282Y +/+ HH subjects (25M, 10 F) were compared with 35 demographically-matched whole blood (WB) donor (non-HH) controls. HH was diagnosed by biochemical and genetic testing. Liver biopsy (n=12) was restricted to subjects at high risk for advanced liver disease Mean initial ferritin level was 1400 ± 1100 ng/mL and transferrin saturation 80 ± 15% in the HH cohort. BMD was measured 4.8 ± 6 (range 0 to 22) yrs after diagnosis using dual energy x-ray absorptiometry (Delphi Advanced Instrument, Hologic, MA), and reported according to absolute bone density (g/cm2), T score (number of SD from peak BMD of persons of the same gender/race) and Z score (number of SD from mean BMD of age-matched persons of the same gender/race). Additional laboratory assessments were performed at the time of BMD testing.Results: HH and WB subjects had similar age (53 vs 54 yr), weight (88 vs 86 kg), gender (71% M), and racial (100% Caucasian) distributions. There were 6 post-menopausal women in each group (8 vs 5 yrs post, p = 0.46). 89% of HH subjects (21/25 men, 10/10 women) and 100% of WB subjects met eligibility criteria for allogeneic blood donation. Mean Z scores were ≥ zero (above age, gender and race adjusted mean values of a reference database maintained by the instrument manufacturer) in both groups at all sites assessed. Absolute BMD values (g/cm2) were similar at the AP spine (1.06 vs 1.04), femoral neck (0.83 vs 0.81), hip trochanteric region (0.77 vs 0.77), total hip (1.00 vs 1.01) and distal radius (0.76 vs 0.75) in HH vs WB subjects (p > 0.25 for all). Respective Z scores at these sites were also similar (0.41 vs 0.39, 0.20 vs 0.08, 0.19 vs 0.49, 0.19 vs 0.46 and 0.45 vs 0.12). Z scores were significantly lower in HH than in WB subjects only at the hip intertrochanteric region (0.14 vs 0.51, p = 0.03); absolute BMD levels at this site were similar (1.16 vs 1.20 g/cm2, p = 0.2). Two HH subjects, including one with cirrhosis, and one WB subject had osteoporosis (T score ≤ −2.5), while 7 HH (20%) and 14 WB (40%) had osteopenia (T score ≤ −1.0) Higher ferritin levels at diagnosis were associated with lower BMD Z scores in univariate logistic regression analysis (p<0.03, all sites tested), however this association remained statistically significant in multivariate analysis only at the total hip region (p=0.008) There were no significant differences in bone specific alkaline phosphatase (65 vs 67 ug/L), osteocalcin (5.5 vs 5.1 ng/mL), ionized and total calcium (1.30 vs 1.30, 2.31 vs 2.31 mmol/L), parathyroid hormone (39 vs 35 pg/mL), 25 OH vitamin D (28 vs 24 ng/mL) or free and total testosterone (113 vs 93 and 313 vs 334 ng/dL, p=0.41 and 0.45, male subjects only) in the HH vs WB study groups.Conclusion: In this study, there was no evidence of clinically significant abnormalities in bone mineral density or in chemical measures of bone metabolism in healthy HH subjects when compared with appropriate age, gender, and racially matched control populations.

Evaluation of the hemodynamics of the femoral head compared with the ilium, femoral neck and femoral intertrochanteric region in healthy adults: Measurement with positron emission tomography (PET)

Non-traumatic osteonecrosis of the femoral head (ONF) is considered to be a disease that occurs primarily due to ischemia of the femoral head, while its etiology and pathology are not fully understood. It is therefore necessary to identify the characteristics of the hemodynamics of the femoral head. In this study, the hemodynamics in the ilium and proximal regions of the femur, including the femoral head, was investigated using positron emission tomography (PET). The subjects of this study consisted of 8 hip joints of four healthy male adults and 3 hip joints on the contralateral side of a femoral neck fracture, avulsion fracture of the greater trochanter and coxarthrosis (1 case each, all females) for a total of 11 hip joints of 7 subjects. The ages of the subjects ranged from 25 to 87 years (average age: 54 years). Blood flow was measured by means of the H215O dynamic study method and blood volume was measured by means of the 15O-labeled carbon monoxide bolus inhalation method. Blood flow was determined to be 9.1 +/- 4.8 ml/min/100 g in the ilium and among proximal regions of the femur (femoral head, neck and intertrochanteric region), 1.8 +/- 0.7 ml/min/100 g in the femoral head, 2.1 +/- 0.6 ml/min/100 g in the femoral neck, and 2.6 +/- 0.7 ml/min/100 g in the intertrochanteric region. In addition, blood volume was 4.7 +/- 1.3 ml/100 g in the ilium, and among proximal regions of the femur, 1.1 +/- 0.5 ml/100 g in the femoral head, 2.1 +/- 0.7 ml/100 g in the femoral neck, and 2.6 +/- 0.9 ml/100 g in the intertrochanteric region. The results showed that both blood flow and volume were lowest in the femoral head. Blood flow and volume were significantly lower in the proximal regions of the femur (femoral head, neck and intertrochanteric region) than in the ilium (p < 0.01). The present study demonstrated that the femoral head is in a hypoemic state as compared with other osseous tissue, indicating that even the slightest exacerbation of hemodynamics in the femoral head can trigger an ischemic condition culminating in ONF.

Effect of Hormone Replacement, Alendronate, or Combination Therapy on Hip Structural Geometry: A 3-Year, Double-Blind, Placebo-Controlled Clinical Trial

This study examined the effect of hormone replacement, alendronate, or combination therapy on hip structural geometry in 373 postmenopausal women over 3 years. We found that antiresorptive agents alone or in combination result in improvement in parameters of hip structural geometry and BMD. These data provide additional information regarding potential mechanisms for fracture reduction with antiresorptive therapy. Fracture reduction is only partially explained by increased BMD. The aim of this study was to examine changes in structural geometry of the hip, derived from DXA in postmenopausal women after treatment with antiresorptive agents. This was a double-blind, placebo-controlled, randomized clinical trial of 373 women over the age of 65 years, who were randomized to hormone replacement therapy, alendronate, combination therapy, or placebo for 3 years. The outcomes included the DXA-derived hip structure analysis program by Beck, which is an engineering interpretation of the DXA data. The indices included cross-sectional area, section modulus (a measure of bending strength), outer diameter, cortical thickness, and buckling ratio (an index of cortical bone stability). Properties were measured in cross-sectional regions traversing the femur at the narrowest point on the femoral neck, the intertrochanteric region, and the proximal shaft. In the femoral neck, improvement in the hip structure analysis indices were generally significantly greater with combination therapy than either monotherapy; increases were also greater at the intertrochanter compared with hormone replacement therapy. For example, the section modulus at the intertrochanter and narrow neck increased 10.6% and 10.3%, respectively, with combination therapy, 9.1% and 7.3% with alendronate, 5.8% and 6.9% with hormone replacement therapy, and 3.4% and 3.2% with placebo (p < 0.01 across the four groups). Buckling ratio increased, suggesting decreased stability in the placebo group, whereas there was either no change or significant improvements (p < 0.05) in each active treatment group. We conclude that changes in the distribution of bone mass underlying the improvements in density with antiresorptive agents in combination or alone have positive effects on structural strength and stability at the proximal femur. This study provides additional information on the potential mechanisms for fracture reduction with antiresorptive agents.