Charles R. Wilson

Adiposity, Fat Distribution, and Cardiovascular Risk

STUDY OBJECTIVE To determine the relative importance of adiposity and fat distribution to cardiovascular risk profile. DESIGN A cross-sectional study. SETTING Clinical research center funded by the National Institutes of Health. PATIENTS Convenience sample of 33 healthy premenopausal women with a wide range of body weight who did not have diabetes mellitus, hirsutism and virilism, gynecologic disorder, cardiac disease, or hypertension. Women participating in exercise or dietary programs or taking medication were excluded. All subjects completed the study. INTERVENTIONS Total body fat mass was determined by hydrostatic weighting, and fat distribution was assessed by subscapular skinfold thickness, subscapular-to-triceps skinfold ratio, the waist-to-hip ratio, and computed tomography. Cardiovascular risk was assessed by the serum insulin response during oral glucose stimulation; levels of triglycerides and total cholesterol; high-density lipoprotein cholesterol to total cholesterol concentrations; and systolic and diastolic blood pressures. MEASUREMENTS AND MAIN RESULTS The anthropometric parameters chosen were significantly associated with the cardiovascular risk profile (P less than 0.001). Visceral fat distribution assessed by computed tomography accounted for a significantly greater degree of variance in the cardiovascular risk factors than the total body fat mass (P less than 0.05). The cumulative insulin response was the primary metabolic variable relating the anthropometric indices to cardiovascular risk. CONCLUSIONS Intra-abdominal fat deposition constitutes a greater cardiovascular risk than obesity alone. Hyperinsulinemia may constitute an important component of the increased cardiovascular risk of abdominal obesity.

Precision assessment and radiation safety for dual-energy X-ray absorptiometry: position paper of the International Society for Clinical Densitometry.

Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis, assess the risk of fracture, and monitor changes in BMD over time. Because biological changes in BMD are usually small in proportion to the error inherent in the test itself, interpretation of serial BMD tests depends on knowledge of the smallest change in BMD that is beyond the range of error. This value, called the least significant change (LSC), varies according to the instrument used, the patient population being tested, the measurement site, the skill of the technologist at positioning the patient and analyzing the test, and the confidence interval used in the calculation. The precision and LSC values provided by the manufacturer cannot be applied to clinical bone densitometry centers because of the differences in the patients being tested and the technologist performing the test. Because harmful errors in clinical management may occur from incorrectly interpreting serial BMD tests, it is recommended that every DXA technologist conduct a precision assessment and calculate the LSC for each measurement site and DXA instrument used. Precision assessment provides direct benefit to patients by allowing clinicians to make clinical decisions based on genuine change or stability of BMD. The patient-care benefits of precision assessment outweigh the risk of exposure to trivial doses of ionizing radiation.

A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part I.

The study presented here investigated hydroxyapatite biomaterials implanted in soft-tissue sites in adult sheep to determine whether these materials are osteoinductive and whether the rate of osteoinduction can be increased by manipulating the composition and porosity of the implants. For the study, 16.8-mm x 5-mm discs were prepared from mixtures of hydroxyapatite and beta-tricalcium phosphate. Five mixtures of hydroxyapatite-ceramic and hydroxyapatite-cement paste forms were studied: 100 percent hydroxyapatite-ceramic (Interpore), 60 percent hydroxyapatite-ceramic, 100 percent hydroxyapatite-cement paste, 60 percent hydroxyapatite-cement paste, and 20 percent hydroxyapatite-cement paste. Biomaterials were implanted in subcutaneous and intramuscular soft-tissue pockets in 10 adult sheep. Cranial bone grafts of equal dimension were implanted as controls. One year after implantation, the volume of all biomaterials and bone grafts was determined from a computed tomographic scan, and porosity and bone formation were determined using backscatter electron microscopy. Cranial bone and the 20 percent hydroxyapatite-cement paste implants demonstrated significant volume reduction in all sites after 1 year (p < 0.001). No significant difference in volume of the remaining four biomaterials was found. There was no significant change in pore size in the ceramic implants (range, 200 to 300 micro) and in the cement-paste implants containing 60 percent hydroxyapatite or more (range, 3 to 5 nm). Pore size in the cement-paste implants containing 20 percent hydroxyapatite increased significantly with resorption of the tricalcium-phosphate component, reaching a maximum of 200 to 300 micro in the periphery, where the greatest tricalcium-phosphate resorption had occurred. Both ceramic biomaterials demonstrated lamellar bone deposition within well-formed haversian systems through the entire depth of the implants, ranging from a mean of 6.6 percent to 11.7 percent. There was minimal bone formation in the cement-paste implants containing 60 percent hydroxyapatite or more. In contrast, cement-paste implants containing 20 percent hydroxyapatite demonstrated up to 10 percent bone replacement, which was greatest in the periphery of the implants where the greatest tricalcium-phosphate resorption had occurred. This study confirms the occurrence of true osteoinduction within hydroxyapatite-derived biomaterials, when examined using backscatter techniques. In this study, the rate of osteoinduction was greatest when a porous architecture was maintained, which was best achieved in ceramic rather than cement-paste forms of hydroxyapatite. Porosity and resultant bone formation in cement-paste implants can be improved by combining hydroxyapatite with a rapidly resorbing component, such as tricalcium phosphate.

Prevalence of the Female Athlete Triad in High School Athletes and Sedentary Students

Objective:To determine the prevalence of the female athlete triad (low energy availability, menstrual dysfunction, and low bone mineral density) in high school varsity athletes in a variety of sports compared with sedentary students/control subjects. Design:Prospective study. Setting:Academic medical center in the Midwest. Participants:Eighty varsity athletes and 80 sedentary students/control subjects volunteered for this study. Intervention:Subjects completed questionnaires, had their blood drawn, and underwent bone mineral density testing. Main Outcome Measures:Each participant completed screening questionnaires assessing eating behavior, menstrual status, and physical activity. Each subject completed a 3-day food diary. Serum hormonal, thyroid-stimulating hormone, and prolactin levels were determined. Bone mineral density and body composition were measured by dual-energy x-ray absorptiometry. Results:Low energy availability was present in similar numbers of athletes (36%) and sedentary/control subjects (39%; P = 0.74). Athletes had more menstrual abnormalities (54%) compared with sedentary students/control subjects (21%) (P < 0.001). Dual-energy x-ray absorptiometry revealed that 16% of the athletes and 30% of the sedentary/control subjects had low bone mineral density (P = 0.03). Risk factors for reduced bone mineral density include sedentary control student, low body mass index, and increased caffeine consumption. Conclusions:A substantial number of high school athletes (78%) and a surprising number of sedentary students (65%) have 1 or more components of the triad. Given the high prevalence of triad characteristics in both groups, education in the formative elementary school years has the potential to prevent several of the components in both groups, therefore improving health and averting long-term complications.

Biomechanical analysis of thoracolumbar interbody constructs. How important is the endplate

Study Design A biomechanical study of human cadaveric thoracic vertebral bodies was conducted using several anterior fusion options subjected to axial loads. This study emphasized the contribution of the endplate to resistance of graft subsidence. Objectives To determine the importance of the vertebral endplate in resisting subsidence of various constructs into the vertebral body; the relative efficacy of potential alternative graft constructs such as iliac crest, ribs, humerus, and titanium mesh cage; and the importance of bone mineral content, vertebral level, and cross‐sectional graft area on construct subsidence. Summary of Background Data As the fixation length of anterior and posterior spinal constructs is reduced, load sharing of the anterior column has become more important to reduce failure of the shorter devices. Several alternative graft constructs and surgical techniques have been used for reconstruction of the anterior column. There exist little comparative data as to whether any of these constructs are superior and whether the vertebral endplate contributes significantly to the integrity of the construct. Methods Sixty‐three isolated human cadaveric vertebral bodies from T3 to T12 were used to test seven different constructs in direct axial load onto prepared endplates with an electrohydraulic testing device. These constructs were: 1) titanium mesh cage (17 × 22 mm) on intact endplate, 2) C‐shaped humerus on intact endplate, 3) tricorticated iliac graft in “tee configuration” on intact endplate, 4) tricorticated iliac graft in cancellous trough, 5) triple rib strut graft, 6) single rib on endplate, and 7) single rib on cancellous body. Dual X‐ray absorptiometry assessment of bone mineral content was performed. A uniaxial load was applied with force and displacement data collected to determine maximal load to “failure” of the vertebral body. Results Preservation of vertebral endplate did not significantly increase the resistance to graft subsidence. The titanium cage construct provided the greatest resistance to axial load. Conclusions Preservation of the vertebral endplate may not offer a significant biomechanical advantage in reconstructing the anterior column. Several alternative constructs are mechanically equivalent.

Association of Dehydroepiandrosterone Sulfate, Body Composition, and Physical Fitness in Independent Community-Dwelling Older Men and Women

OBJECTIVES: To determine the association of dehydroepiandrosterone sulfate (DHEAS), body composition, and physical fitness in independent community‐dwelling men and women aged 60 to 80 years.

Functional biomechanics of the thoracolumbar vertebral cortex.

Studies were conducted on human cadaver thoracolumbar vertebrae, at the T12-L5 level, of five males and six females. Isolated vertebral bodies, free of posterior elements, were first scanned using dual photon absorptiometry and then underwent axial compressive loading. All of the vertebral bodies failed as a result of compressive fractures of the bone. Results indicated that the mechanical load-deflection response was non-linear and biphasic. The mean cross-sectional areas of the vertebral bodies progressively increased from L1, to L5. The maximum load carrying capacity was not dependent upon spinal level. The bone mineral content (BMC) obtained using dual photon absorptiometry in the lateral projected plane increased from L, to L5. Male vertebral bodies consistently had higher BMC than female specimens. The cortical shell contributed 12·44% (mean) of the total cross-sectional area in the male, 17·56% in the female; 8·85% of the BMC in the male and 1654% in the female. In contrast, it accounted for 43·8% (mean) of the total load in the male compared to 35·2% in the female specimens. Mean failure loads of decorticated vertebrae were significantly lower (p<0.001) when compared with that of the adjacent intact vertebral bodies. In one osteoporotic spine, the cortical shell accounted for 74% of the total strength. The anatomical placement of the thin shell which enables it to act as an encasing element to resist the collapse of the trabeculae under compression, and the difference in rigidity of the two structural components, and their differing sensitivity to metabolic influences, seem to explain this relatively high magnitude of load absorption in spite of its limited contribution to vertebral geometry.

Is There an Association between Athletic Amenorrhea and Endothelial Cell Dysfunction

PURPOSE To test the hypothesis that young females with athletic amenorrhea and oligomenorrhea show signs of early cardiovascular disease manifested by decreased endothelium-dependent dilation of the brachial artery. METHODS Ten women with athletic amenorrhea (mean +/- SE, age 21.9 +/- 1.2 yr), 11 with oligomenorrhea (age 20.8 +/- 1.1 yr), and 11 age-matched controls (age 20.2 +/- 1.1 yr) were studied. Study subjects were amenorrheic an average of 2.3 (range 0.6-5) yr and oligomenorrheic an average of 6.2 yr. All ran a minimum of 25 miles.wk. They were nonpregnant and free of metabolic disease. Brachial artery flow-mediated dilation (endothelium-dependent) was measured with a noninvasive ultrasound technique in each group. RESULTS Endothelium-dependent brachial artery dilation was reduced in the amenorrheic group (1.08 +/- 0.91%) compared with oligomenorrheic (6.44 +/- 1.3%; P< 0.05) and eumenorrheic (6.38 +/- 1.4%; P< 0.05) groups. CONCLUSION Athletic amenorrhea is associated with reduced endothelium-dependent dilation of the brachial artery. This may predispose to accelerated development of cardiovascular disease.

A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part II. Bioengineering implants to optimize bone replacement in reconstruction of cranial defects.

The present study investigated hydroxyapatite biomaterials implanted in critical-size defects in the calvaria of adult sheep to determine the optimal bioengineering of hydroxyapatite composites to facilitate bone ingrowth into these materials. Five calvarial defects measuring 16.8 mm in diameter were made in each of 10 adult sheep. Three defects were filled with cement paste composites of hydroxyapatite and beta-tricalcium phosphate as follows: (1) 100 percent hydroxyapatite-cement paste, (2) 60 percent hydroxyapatite-cement paste, and (3) 20 percent hydroxyapatite-cement paste. One defect was filled with a ceramic composite containing 60 percent hydroxyapatite-ceramic, and the fifth defect remained unfilled. One year after implantation, the volume of all biomaterials was determined by computed tomography, and porosity and bone replacement were determined using backscatter electron microscopy. Computed tomography-based volumetric assessment 1 year after implantation demonstrated that none of the unfilled cranial defects closed over the 1-year period, confirming that these were critical-size defects. There was a significant increase in volume in both the cement paste and ceramic implants containing 60 percent hydroxyapatite (p < 0.01). There was no significant change in volume of the remaining cement paste biomaterials. Analysis of specimens by backscatter electron microscopy demonstrated mean bone replacement of 4.8 +/- 1.4 percent (mean +/- SEM) in 100 percent hydroxyapatite-cement paste, 11.2 +/- 2.3 percent in 60 percent hydroxyapatite-cement paste, and 28.5 +/- 4.5 percent in 20 percent hydroxyapatite-cement paste. There was an inverse correlation between the concentration of hydroxyapatite and the amount of bone replacement in the cement paste for each composite tested (p < 0.01). Bone replacement in 60 percent hydroxyapatite-ceramic composite (13.6 +/- 2.0 percent) was not significantly different from that in 60 percent hydroxyapatite-cement paste. Of note is that the ceramic composite contained macropores (200 to 300 microm) that did not change in size over the 1-year period. All cement paste composites initially contained micropores (3 to 5 nm), which remained unchanged in 100 percent hydroxyapatite-cement paste. Cement paste implants containing increased tricalcium phosphate demonstrated a corresponding increase in macropores following resorption of the tricalcium phosphate component. Bone replacement occurred within the macropores of these implants. In conclusion, there was no significant bone ingrowth into pure hydroxyapatite-cement paste (Bone Source, Stryker-Leibinger Inc., Dallas, Texas) in the present study. The introduction of macropores in a biomaterial can optimize bone ingrowth for reconstruction of critical-size defects in calvaria. This was demonstrated in both the ceramic composite of hydroxyapatite tested and the cement paste composites of hydroxyapatite by increasing the composition of a rapidly resorbing component such as beta-tricalcium phosphate.

The effect of positioning on dual energy X-ray bone densitometry of the proximal femur.

The influence of subject repositioning on the precision of bone mineral densitometry of the proximal femur using dual energy X-ray absorptiometry was estimated by determining the variation in the bone mineral density (BMD) of subjects scanned with their foot and leg position varying from that routinely used in clinical scanning. The mean variations in BMD of the femoral neck, Wards triangle and trochanter were 2.7, 4.1 and 1.7%, respectively, in eight subjects scanned with the foot internally rotated by 0, 13 and 27 degrees. The mean variations in BMD in four subjects scanned with the leg in the customary position and abducted +/- 6 degrees from the conventionally used scanning position were 3.6, 2.8 and 1.6% for the same respective regions of interest. For diagnostic applications, the orientation of the leg and foot during scanning is relatively unimportant since the variations in BMD introduced by the different foot and leg orientations likely to be encountered in routine clinical scanning are small compared to the intrapopulation variation in BMD. However, for monitoring changes in BMD longitudinally, careful repositioning of the foot and leg will be necessary to achieve precision in vivo of less than 1%.