Surrogate markers of visceral adipose tissue in treated HIV-infected patients: accuracy of waist circumference determination.

OBJECTIVES: The accuracy of the use of anthropometrics to quantify visceral adipose tissue (VAT) in treated HIV-infected patients is unknown. We evaluated the predictive accuracy of waist circumference (WC) with and without dual-energy X-ray absorptiometry (DXA)-derived trunk : limb fat ratio [fat mass ratio (FMR)] as surrogates for VAT determined using computerized axial tomography (CT-determined VAT). METHODS: We performed a retrospective cohort analysis of treated HIV-infected male patients followed at the Modena HIV Clinic. We developed prediction equations for VAT using linear regression analysis and Spearman correlations. Receiver operating characteristic (ROC) analysis evaluated the accuracy of WC alone or with FMR at discrete VAT thresholds. RESULTS: The 1500 Caucasian male patients had a median age of 45 years, body mass index (BMI) of 24, WC of 87 cm, VAT area of 127 cm(2) and body fat percentage of 14%. The correlation between WC-predicted VAT and CT-VAT was 0.613, and this increased significantly if FMR was added. The WC-associated R(2) of 0.35 increased to 0.51 if the prediction equation included WC plus FMR. The area under the ROC curve (AUC) using WC was 0.795-0.820 at all VAT thresholds. The positive predictive value (PPV) and negative predictive value (NPV) changed reciprocally at CT-VAT thresholds from 75 to 200 cm(2) and ranged from 0.72 to 0.74, respectively, at a representative VAT of 125 cm(2). Adding the FMR to the predictive equations increased the AUC in the range of 0.854-0.889 with the PPV and NPV increasing minimally, ranging from 0.780 to 0.821. Limits of precision were wide, especially at the highest CT-VAT levels, and varied from 24 to 68 cm(2). CONCLUSIONS: WC is a limited surrogate for CT-VAT in this population and DXA-derived parameters do not improve performance indices to a clinically relevant level. These findings should inform the applicability of WC to predict VAT in treated HIV-infected male patients.

Ability of peripheral DXA measurement to diagnose osteoporosis as assessed by central DXA measurement.

In order to evaluate the utility of peripheral measurement of bone mineral density (BMD) in the diagnosis of osteoporosis, we measured BMD at the spine and femoral neck with central dual-energy X-ray absorptiometry (DXA), at phalanx with AccuDXA (Schick) as well as proximal and distal forearm with pDXA (Norland) in 835 women ranging in age from 20 to 85 yr. In receiver operating characteristic (ROC) curves, where a positive case was defined as a T-score < or = -2.5 either on spine or femoral neck, the areas under the curve were not significantly different between sites. At a T-score of -2.5 as determined by each peripheral apparatus, sensitivity and specificity were, respectively, 0.39 and 0.95 for phalanx and 0.75 and 0.85 for proximal forearm whereas they were 0.42 and 0.96 for distal forearm. Using optimal absolute BMD cutoff values improved the results. Sensitivity and specificity were, respectively, 0.79 and 0.83 for phalanx at an absolute BMD value of 0.436 and 0.84 and 0.79 for proximal forearm at a value of 0.703, whereas they were 0.90 and 0.75 for distal forearm at a value of 0.208. Combining the two forearm measurements improves the results slightly. At cutoff values of 0.641 and 0.252, respectively for proximal and distal forearms, sensitivity was 0.83 and specificity was 0.84. Therefore, a peripheral measurement of BMD together with a good clinical evaluation of the osteoporosis risk profile of the patient, can be an interesting tool for the diagnosis of osteoporosis in areas where central DXA is not available.

A crossover comparison of four peripheral bone-site measurements to identify central osteopenia and osteoporosis in women.

The objective of this study was to assess the ability of four peripheral bone measurement sites to predict low bone mineral density of the lumbar spine, femoral neck, and total hip as defined by the WHO classification, and to evaluate their role as a screening procedure for central dual-energy X-ray absorptiometry (DXA). One thousand three hundred white women patients aged 58.3+/-13.9 years were enrolled. Correlations between the peripheral and central sites were moderate, varying between 0.51 and 0.67. In receiver-operating characteristic (ROC) analysis, the areas under the curve for the peripheral sites revealed a few small, but significant, differences between sites. The optimal cut-point was derived from the ROC data for each site to assess its value as a screening parameter. These proved to be unsatisfactory, because the average number of false positives and false negatives were 18% and 24%, respectively. A proposal is made which entails two cut-points, one for an acceptable percentage of false negatives and the other for an acceptable number of false positives. Patients with t-scores between these cut-points would be referred for central DXA for classification. The result is a substantial decrease in the number of false negatives, i.e., patients who would be candidates for treatment. The contentious issue is what proportion of supplemental DXAs is considered logistically and economically acceptable for any of the peripheral site measurements to be useful.

Femoral remodeling after porous-coated total hip arthroplasty with and without hydroxyapatite-tricalcium phosphate coating: a prospective randomized trial.

We prospectively assessed femoral bone remodeling using dual-energy x-ray absorptiometry for 2 years after total hip arthroplasty. Thirty-nine hips were randomized to receive a titanium proximally porous-coated femoral component with or without hydroxyapatite-tricalcium phosphate coating. Although both stems resulted in alterations in the periprosthetic bone mineral density, the hydroxyapatite-tricalcium phosphate coated stems had significantly less femoral bone loss than the uncoated stems at 2-year follow-up. This reduced femoral bone loss may provide short-term and long-term advantages over noncoated stems.

Periprosthetic bone densitometry of the hip: influence of prosthetic design and hydroxyapatite coating on regional bone remodelling.

OBJECTIVE: To determine the influence of femoral hip prosthesis design and composition on regional periprosthetic bone remodelling as a function of time in asymptomatic patients. MATERIALS AND METHODS: Bone mineral density (BMD) changes surrounding two differently designed porous-coated femoral prostheses (S-ROM, n=111; and Multilocki, n=62) were determined serially over a 24 month interval. There was a subset of patients with Multilock implants that were coated with a 50 micron film of hydroxy-apatite (n=23) over the porous surface. Seven Gruen zones defined the periprosthetic bone regions (LUNAR ORTHO software). Inclusion criteria were primary implants, Harris hip scores >or=95 and no radiographic evidence of loosening. RESULTS: For the S-ROM femoral component, at 6 months all zones showed a significant decrease in BMD relative to the immediate postoperative baseline measurements; mean loss varied from 4.3% to 17.4%. At 24 months mineral change varied from -10.8% to +1% for Gruen zones 1 to 6. Gruen zone 7, the calcar, differed in that it was the site of greatest mineral loss, attaining a mean of 17% at 24 months, and it was also significantly greater than the losses registered in the other zones at that time point. For the Multilock, maximal mineral losses were registered at zones 1 and 7. There were significant differences in mineral losses between the S-ROM and Multilock implants in zones 1, 2 and 3 at 24 months; S-ROM losses of 7.3%, 10.8% and 3.5% respectively, compared to Multilock losses of 23.8%, 15.9% and 6.9% respectively. Comparison of hydroxyapatite coated and uncoated Multilock implants demonstrated significantly less loss in the coated implants in zones 1 (greater trochanter) and 7 at 24 months. Coated losses were -16.9% and 11.3% for zones 1 and 7, respectively, whereas uncoated losses were 23.8% and 20.5% respectively.

Temporal changes of periprosthetic bone density in patients with a modular noncemented femoral prosthesis.

Bone mineral density changes surrounding a porous-coated proximal modular sleeved hip prosthesis were determined as a function of time over a 24-month period. The periprosthetic bone regions were defined by the 7 Gruen zones. Measurements were obtained with a dual-energy x-ray densitometer using a dedicated software program. Inclusion criteria required that the patients had primary implants, were asymptomatic with Harris hip scores of > or =95 for the duration of the study, and showed no radiographic evidence of loosening. The protocol specified that bone measurements be obtained within 1 week after surgery as a baseline reference and at 3, 6, 9, 12, 18, and 24 months thereafter. A total of 111 consecutive patients were enrolled in this ongoing prospective study, of whom 52 had 4 or more measurements after the initial baseline determination for statistical analysis. At 3 months, all zones showed a significant decrease in bone mineral density relative to the baseline measurements, and their mean loss ranged from 6.5% to 11.2%. By 24 months, mineral losses relative to baseline varied from 0 to 11% for Gruen zones 1 to 6. Relative to the 3-month levels, there was no significant change in zones 1, 4, and 6; a significant improvement in zones 3 and 5; and a small but significant loss in zone 2 at 24 months. Gruen zone 7, the medial femoral neck cortex, differed in that it was the site of greatest bone mineral loss, attaining a mean of 20.2% at 24 months. It was found that the amount of periprosthetic mineral loss at 12 months was independent of the initial baseline reference bone mineral levels. Results of this study show the normal temporal bone mineral changes surrounding a proximally modular porouscoated femoral implant. The pattern of change demonstrated may be peculiar to the prosthesis used in this study because it might differ in implants of different design and material composition.

Calcaneal ultrasonometry: response to treatment in comparison with dual x-ray absorptiometry measurements of the lumbar spine and femur.

The object of this study was to determine the effectiveness of calcaneal ultrasonometry in the prediction of bone mineral changes in the lumbar spine and femoral neck in response to treatment of osteoporosis. There were 673 women in the study who had one or more follow-up measurements between 1 and 4 years after the initial baseline determination for a total of 881 same-day measurements of the calcaneus, spine, and femur. The LUNAR Achilles and LUNAR DPX (LUNAR Corporation, Madison, WI) were used. Patients were divided into three treatment time groups: Group 1, 1-<2 years, n = 461; Group 2, 2-<3 years, n = 278; Group 3, 3-<4 years, n = 142. There were significant increases in the bone mineral density (BMD) of the lumbar spine, femoral neck, and in the broadband ultrasonic attenuation (BUA) of the calcaneus for the three groups. In contrast, a significant decrease in speed of sound (SOS) was obtained in these time frames and the stiffness index remained unchanged. Spearmen correlations showed an inverse relationship between the percent changes in SOS and BUA, the reasons for which are speculative. Correlations between the percent changes in calcaneal parameters and the BMDs of the lumbar spine and femoral neck were weak, whether significant or not, rho varying from -0.12 to 0.20. There was a subset of 371 patient measurements that registered BMD increases in both the lumbar spine and femoral neck. This was considered to be an objective indication of adequate compliance with prescribed treatment. Analysis of this subset yielded parameter correlations similar to those of the entire group. It is concluded that changes in the calcaneal ultrasound parameters in response to treatment of osteoporosis are not a reflection of mineral changes occurring in the lumbar spine and femoral neck in a given individual, and in this regard, calcaneal ultrasonometry is not a substitute for direct-site dual X-ray absorptiometry (DXA) measurement of the lumbar spine and femur.

Bone densitometry: influence of prosthetic design and hydroxyapatite coating on regional adaptive bone remodelling.

The objective of this prospective study was to determine if bone densitometry can detect disparities in regional adaptive bone remodelling surrounding the cementless porous-coated femoral component of a hip prosthesis in two titanium alloy implants of different design . These prostheses were the S-ROM (n=69) and the Multilock (n=65). The Multilock implants consisted of two groups; 25 had a 50 micron layer of hydroxyapatite (HA) sprayed over the porous surface of the femoral component and the remaining 40 femoral components were not coated with HA. Densitometry was performed with dual energy X-ray absorptiometry (DXA) utilizing the LUNAR ORTHO software to analyse the seven Gruen zones. Bone mineral density measurements were obtained within a week of surgery as a baseline reference and at 6, 12, 24, 36 and 48 months thereafter. At 6 months there was significant mineral loss in all Gruen zones in the three prostheses. By 48 months there were differences in mineral loss between the three prostheses. In the zones adjacent to the porous surface, predominantly zones 1 and 7, the S-ROM exhibited 60% less mineral loss than the Multilock in zone 1, and there was no significant difference in zone 7. Compared to the Multilock-HA, the S-ROM lost 35% less mineral in zone 1, but the Multilock lost 70% less mineral than the S-ROM in zone 7. The Multilock-HA lost 37% and 75% less mineral than the Multilock in zones 1 and 7, respectively, i.e., hydroxyapatite coating tended to preserve bone stalk. Using the Gruen zone area measurements provided by the software, the S-ROM had significantly greater bone resorption in zone 7 at 24 months than either of the Multilocks, which did not differ from each other. In conclusion, DXA has shown differences in periprosthetic adaptive bone remodelling between implants of different design and composition as a function of time.

Hip and knee prostheses: evaluation of the natural history of periprosthetic bone changes.

This is a review of normal adaptive bone remodeling in response to hip and knee endoprostheses as manifested by changes in regional bone mineral density and radiophosphate uptake as a function of time. The normal evolution of change may vary with the design and composition of the implant. Appreciation of the normal temporal alterations enhances the ability to disclose prosthetic complications, but it is not without its limitations. The literature reports on the efficacy of radiophosphate to detect implant loosening are variable and differ between those that are cemented and not.

Influence of bone quality on precision of calcaneal ultrasonometry.

This study was designed to determine the changes in precision of the ultrasound parameters speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) as a function of bone quality. The instrument used in this investigation was the LUNAR Achilles. Of the 608 female patients who had paired measurements with repositioning, 200 had t scores >/=-1 and 408 had t scores

Selective supplementation of calcaneal ultrasound densitometry with dual-energy x-ray absorptiometry of the spine and femur for population screening.

OBJECTIVE: To determine the limitations on the improvements in the efficacy of screening with ultrasound densitometry of the calcaneus that can be achieved by adding direct-site mineral measurements of the lumbar spine and the femur when the ultrasound t-score is low. SUBJECTS AND METHODS: The author retrospectively analysed data from 2500 women for whom the results of both dual-energy x-ray absorptiometry of the lumbar spine and femur and ultrasonometry of the calcaneus were available. Various ultrasound t-score cut-off values (from 0 to -4.5) were tested to determine changes in sensitivity, specificity, false negatives, false positives and accuracy with and without adding direct-site measurements of the lumbar spine and the femur neck. RESULTS: For this analysis, the addition of direct-site measurement data increases the specificity to 100% for all t-score cut-off values without affecting the sensitivity, thereby improving the accuracy; however, the number of false negatives remains unknown. The number of false negatives decreases as the cut-off value is increased, but with higher cut-off values, greater numbers of subjects would have to be recalled for direct-site measurements of the lumbar spine and the femoral neck, which would entail extra costs. CONCLUSIONS: The accuracy of screening for low mineral content by calcaneal ultrasonometry is improved by recalling subjects for direct-site measurements if their ultrasound t-score falls below some arbitrary value. The cut-off value must be chosen to achieve a balance between the number of missed false negatives that are acceptable in the screening process and the number of subjects recalled for the direct-site study at additional cost. In remote areas, where dual-energy x-ray absorptiometry devices for performing the supplemental measurement are not usually available, the cost of transportation would be another factor.

Correlation of ultrasound velocity in the tibial cortex, calcaneal ultrasonography, and bone mineral densitometry of the spine and femur.

We compared the attributes of tibial cortex speed of sound (SOS) measurements with the SOS and broadband ultrasound attenuation (BUA) of the calcaneus, and bone mineral densities of the lumbar spine and femoral neck in a patient crossover study. The three instruments used in the crossover study were the LUNAR DPX and AchillesTM, and a newly introduced device for measuring tibial cortical SOS, the SoundScanTM 2000. Ultrasound precision determinations on the two instruments were performed with the same group of 10 volunteers, and the bone densitometry precision was derived from 22 patients who were assessed twice in a single visit, with repositioning between spine and hip scans. There were 220 female patients in the clinical study, 28 of whom had thoracic spine fractures, and all had measurements with the three instruments. Of the three instruments, the best precision, or lowest coefficient of variation and standardized coefficient of variation, was obtained with the SoundScanTM 2000; 0.20% and 1.39%, respectively. The tibial SOS correlated more poorly with the lumbar spine and femoral neck bone mineral densities (BMDs) than the calcaneal parameters in 220 patients. Tibial SOS measurements could not distinguish the group with spinal fracture from an age-matched control group to a P < 0.05 level, whereas the lumbar spine BMD and calcaneal BUA and stiffness showed a significant difference. We conclude that the SoundScanTM 2000 system measures propagation of sound in the tibial cortex with great precision, but its role in clinical practice is moot. Yet to be established by a long-term prospective study is its efficacy in predicting fracture risk and how well it reflects bone change in response to treatment of osteoporosis.

Effect of rotation on periprosthetic bone mineral measurements in a hip phantom.

The effect of rotation on the measurement of periprosthetic bone mineral content and bone mineral density using dual energy xray absorptiometry was studied in 9 anatomic specimen femora implanted with noncemented titanium hip prostheses. An apparatus was constructed to permit accurate femoral rotation through an arc of 30 degrees internal to 30 degrees external rotation in 5 degrees increments. Two scans were obtained at each increment of rotation for a total of 26 scans for each implanted femur. Change in bone mineral content and bone mineral density was measured for each of 7 contiguous periimplant regions (Gruen zones). The precision of the paired bone mineral density measurements was 1.7%. In all Gruen zones, the means of bone mineral content and bone mineral density measurements varied within 5% between 15 degrees internal and 15 degrees external rotation. Variation in limb rotation, as might occur with temporal studies of periimplant bone remodeling, can be tolerated within easily controllable limits without excessive error in bone mineral measurements.

A new thrombus imaging agent. Human recombinant fibrin binding domain labeled with In-111.

The amino-terminal domain of fibronectin has a fibrin binding site and a site for covalent cross-linking to fibrin. This fibrin binding domain was isolated from human recombinant fibronectin and labeled with In-111; the final molecular weight was 12 kD. It was applied to a pilot study of 62 patients; 30 who were thought to have deep vein thrombosis and 32 controls. All 30 patients had either impedance plethysmography, duplex ultrasound, contrast venography, or various combinations of the three. Eight disagreements in the 30 patients suspected of having deep vein thrombosis were registered between fibrin binding domain imaging and the other examinations. Three of the patients with negative scan results had clots that were 1 week old or older, and this may be a limitation of the technique. In three other patients who had negative scan results, but positive alternative studies, there was a history of previous episodes of deep vein thrombosis and this could be a cause of false-positive results in the other modalities. There was one documented false-negative scan in a fresh clot. Normal scans were obtained in the lower extremities of the control patients, except in two who demonstrated uptake at the sites of insulin injections. The initial results of this feasibility study are encouraging and warrant further investigation.

A correlative study of ultrasound calcaneal and dual-energy X-ray absorptiometry bone measurements of the lumbar spine and femur in 1000 women.

The objectives of the study were firstly to determine the accuracy of ultrasound calcaneal measurements in the prediction of bone mineral density determinations with dual-energy X-ray absorptiometry (DXA) of the lumbar spine (LS), femoral neck (FN), and Ward's triangle (FW) in a mixed population of 1000 women, unsorted as to diagnosis, and secondly to determine the accuracy of the various site-specific measurements in predicting each other. Ultrasound measurements [stiffness, speed of sound (SOS) and broadband ultrasound attenuation (BUA)] were made with the Lunar Achilles device, and the bone mineral density (BMD) of the LS, FN and FW were determined with the Lunar DPX. The data were analyzed for correlation, sensitivity, specificity, and accuracy of various paired sites. The coefficients of correlation of the young adult t-scores in the total group between calcaneal stiffness and BMDs of the LS, FN, and FW varied between 0.53 and 0.60. Coefficients for LS versus FN and FW were 0.70 and 0.62, respectively. A comparison of SOS and BUA values obtained at the calcaneus with BMDs of the LS, FN and FW yielded correlation coefficients that varied from 0.54 to 0.56. The general accuracy of prediction of one site by another ranged from 64.2% to 74.4%, where normality was defined as a t-score > -2. It is concluded that no site can predict the status of another site with sufficiently high accuracy to be clinically useful. The role of ultrasound transmission in bone as a predictor of fracture risk is theoretically promising, but has yet to be proved by a long term prospective study.

Radiophosphate imaging and bone densitometry in renal osteodystrophy.

The histologic features of renal osteodystrophy vary from dialysis osteomalacia to osteitis fibrosa cystica. Commensurate with this, the number of osteoblasts and osteoclasts changes with the stage of the disease; the osteoblasts are virtually absent in dialysis osteomalacia and are numerous in osteitis fibrosa. Radiophosphate accretion in bone increases with increasing osteoblastic activity, and the bone mineral status is determined by the net difference in osteoblastic and osteoclastic activity. The application of radionuclide imaging and dual radiographic absorptiometry mineral measurements in patients with renal osteodystrophy, renal transplants, and following parathyroidectomy for secondary hyperparathyroidism is reviewed.

DEXA bone densitometry measurements in adults with X-linked hypophosphatemia.

Bone mineral densities in adults with X-linked hypophosphatemia are variable, and while most are reportedly normal some can be very high. Eighteen patients with adult X-linked hypophosphatemia underwent bone mineral determinations of the lumbar spine and femoral neck with dual energy x-ray absorptiometry (DEXA). Most of them were on various treatment regimens. Ten of 18 patients (55%) had spinal bone mineral densities that were greater than two standard deviations above the age-matched mean, and 3 of 11 patients (27%) had bone mineral densities of the femoral neck in excess of two standard deviations. Eight patients (median age 41.5 years) were followed serially for 24 to 42 months, and they exhibited a spinal bone loss of 0.019 gm/cm2/year.

Long-term outcome following total parathyroidectomy in patients with end-stage renal disease.

Long-term follow up (mean 3.8 years), following elective total parathyroidectomy in thirteen patients with end-stage renal disease is described. Nine patients are alive and all except two have measurable levels of intact parathyroid hormone (PTH). One patient is mildly hyperparathyroid with PTH levels of 143 pg/ml (normal 10-65 pg/ml). All patients did well as far as their bone and mineral metabolism were concerned and there were no fractures, bone pain or metastatic soft tissue calcification. Lumbar spine bone mineral density (BMD) increased above the baseline value and femoral neck bone density was significantly greater than a matched control group of non-parathyroidectomized dialysis patients (1.097 +/- 0.140 versus 0.811 +/- 0.148 g/cm2, Z-score 1.98 +/- 1.64 versus -0.79 +/- 1.07, p < 0.001). Two of the nine patients have been transplanted, both have good allograft function and show increases in BMD. We believe that these findings justify the complete removal of all parathyroid tissue for selected patients with chronic renal failure where medical therapy has failed and aluminium bone disease has been excluded. They also raise the possibility that PTH is necessary for bone loss to occur.

Computed tomographic detection of skeletal muscle calcifications in rhabdomyolysis.

The authors report a case of rhabdomyolysis with extensive calcification of the paravertebral muscles secondary to ingestion of desipramine hydrochloride, a tricyclic antidepressant. Computed tomography (CT) and isotope scanning were performed, and pathological confirmation of the condition was obtained. The extent of the calcification was probably due to the administration of supplementary calcium to correct hypocalcemia. The authors discuss the correlation between the CT and isotope scan findings.