Daniel T. Baran

Ultrasound attenuation of the Os calcis in women with osteoporosis and hip fractures

SummaryBone ultrasound attenuation of the calcaneus, and vertebral and femoral bone density measured by dual photon absorption were determined in 22 women with osteoporosis, 10 women with hip fractures, and 29 normal, age-matched controls to determine the utility of the ultrasound technique as an indicator of axial osteopenia. Vertebral and femoral neck density and bone ultrasound attenuation were significantly decreased (P<0.01) in the women with osteoporosis and those with hip fractures. The sensitivity and specificity of bone ultrasound attenuation was 80% at a value of 50 dB/MHz. At 90% specificity the sensitivity of bone ultrasound attenuation was 65%. The results of this pilot study suggest that ultrasound attenuation, a safe, simple, and radiation-free procedure, may be utilized as an indicator of decreased axial bone mass.

Ultrasound attenuation of the calcaneus: a sensitive and specific discriminator of osteopenia in postmenopausal women.

SummaryRecent studies have evaluated techniques for estimating bone mass without radiation. The present study compares broadband ultrasound attenuation of the calcaneus and bone densities of the femoral neck and the lumbar spine in 17 normal women and 41 women with osteoporosis. Twenty of the osteoporotic women had spine (n=16) or femoral neck (n=4) fractures. There was a significant decrease in the broadband ultrasound attenuation (P<0.001) in women with osteoporosis compared with normal women. The osteoporotic women also showed a decrease in vertebral (P<0.0001) and femoral neck (P<0.0001) densities compared with normal women. At 63 dB/MHz, the sensitivity and specificity of broadband ultrasound attenuation for decreased bone mineral density with or without fractures were 76%. All women with fractures had a broadband ultrasound attenuation less than 72 dB/MHz. This corresponded to a specificity of 41%. To determine whether broadband ultrasound attenuation correlated with trabecular bone volume, samples of cadaver calcaneus were analyzed. The histologic determination showed a significant correlation between broadband ultrasound attenuation and trabecular bone volume (r=0.992,P=0.008). These results suggest broadband ultrasound attenuation of the calcaneus reflects bone mass and can be used as a safe and sensitive indicator for decreased axial bone density.

Quantifying bone loss from the proximal femur after total hip arthroplasty

To define the natural history of bone loss around a femoral prosthesis, the bone mineral content and bone mineral density were measured for each femur in 28 patients with unilateral total hip arthroplasty, 18 age-matched controls, and seven patients with unilateral osteoarthritis. The areas measured were inside the lesser trochanter and 4.8 cm distal to it. The contralateral hip served as the control. Three years after arthroplasty there was 40% loss in average bone mineral content inside the lesser trochanter, and 28% loss in average bone mineral content 4.8 cm distally in the medial cortex. At seven to 14 years after operation, patients had lost 40% of bone proximally and 49% distally. The data suggest that this may progress in a proximal-to-distal fashion, and could account for a 50% decrease in bone mass seven to 14 years after surgery.

The relationship between ultrasound and densitometric measurements of bone mass at the calcaneus in women

SummaryBroadband ultrasound attenuation (BUA) of the calcaneus predicts axial density in women and is decreased in women who sustain hip fractures. To determine the relationship between ultrasonic and densitometric assessments of bone mass at the same site, BUA and velocity of sound (VOS) were correlated with bone density as measured by dual energy x-ray absorptiometry (DXA) at the calcaneus in 64 Caucasian women aged 35–83 years. BUA, VOS, and bone density in these women decreased annually as a function of age by 1.0%, 0.3%, and 0.9%, respectively. Holding age, years since menopause, height and weight constant, BUA correlated with VOS (r=0.74, P<0.001), and calcaneal density correlated with BUA (r=0.73, P<0.001) and with VOS (r=0.66, P<0.01). The results indicate that both BUA and VOS measurements reflect density at the calcaneus, but suggest that they measure properties of bone other than density and different from each other. The assessment of these additional properties may be useful in the prediction of fracture risk.

Practical clinical application of biochemical markers of bone turnover: Consensus of an expert panel.

Biochemical markers of bone turnover have emerged as powerful tools to aid in managing osteoporosis. The newer bone markers have been intensively studied for more than a decade. As a result, we can now confidently report their clinical utility in assessing risk of rapid bone loss and fracture, and monitoring therapy in postmenopausal women with or at risk of osteoporosis. In this review, we will provide a comprehensive foundation for this utility. While there are still questions remaining to be answered, bone marker technology has matured to play an essential role in patient management. We will describe, in practical terms, how bone markers can be appropriately incorporated into clinical practice today.

Single X-ray absorptiometry of the forearm: precision, correlation, and reference data.

The performance of a single X-ray absorptiometry (SXA) device incorporating an X-ray tube as a photon source was evaluated with respect to precision in vivo and in vitro, scan time, image quality, and correlation with an existing dual energy X-ray absorptiometry (DXA) device. SXA precision in vivo, expressed as a coefficient of variation (CV), was 0.66% for bone mineral content (BMC) and 1.05% for bone mineral density (BMD). Precision in vitro, based on 78 BMC measurements of a forearm phantom over 195 days, was 0.53%. Correlation with DXA at the 8 mm distal forearm site was high (r=0.97 for BMC and r=0.96 for BMD). A preliminary SXA reference database composed of 151 healthy Caucasian American women was developed to facilitate the interpretation of patient measurements. SXA scan time was 4 minutes and delivered a radiation exposure of 1.68 mrem. SXA image quality and spatial resolution were superior to SPA and comparable to DXA.

Annexin II is the membrane receptor that mediates the rapid actions of 1α,25-dihydroxyvitamin D3†

1α,25‐Dihydroxyvitamin D3 has been shown to exert its effects by both genomic (minutes to hours) and rapid (seconds to minutes) mechanisms. The genomic effects are mediated by interaction with the nuclear vitamin D receptor. We show that the vitamin D analog, [14C]‐1α,25‐dihydroxyvitamin D3 bromoacetate, is specifically bound to a protein (molecular weight 36 kDa) in the plasma membrane of rat osteoblastlike cells (ROS 24/1). The plasma membrane protein labeled with the bromoacetate analog was identified as annexin II by sequence determination and Western blot. Partially purified plasma membrane proteins (PI 6.9–7.4) and purified annexin II exhibited specific and saturable binding for [3H]‐1α,25‐dihydroxyvitamin D3. Antibodies to annexin II inhibited [14C]‐1α,25‐dihydroxyvitamin D3 bromoacetate binding to ROS 24/1 plasma membranes, immunoprecipitated the ligand–protein complex, and inhibited 1α,25‐dihydroxyvitamin D3–induced increases in intracellular calcium in ROS 24/1 cells. The results indicate that annexin II may serve as a receptor for rapid actions of 1α,25‐dihydroxyvitamin D3. J. Cell. Biochem. 78:34–46, 2000.

Insulin‐like growth factor binding proteins in femoral and vertebral bone marrow stromal cells: Expression and regulation by thyroid hormone and dexamethasone

Insulin‐like growth factor (IGF)‐I is an important regulator of bone metabolism. Clinical observations suggest that different anatomic sites within the adult skeleton respond differently to hormonal and therapeutic treatment, and recent studies on bone marrow stromal cells in culture show that there are skeletal site‐dependent differences in the gene expression of IGF‐I. The actions of IGF‐I and ‐II on bone cells are known to be modulated by the IGF binding proteins (IGFBP)‐1 through ‐6 and the Type I and Type II IGF receptors. Therefore, we compared the expression of IGFBP‐1 through ‐6 in adult female rat bone marrow stromal cell cultures derived from two separate skeletal sites: vertebrae and femurs. The cultures were maintained simultaneously under conditions that support osteoblast differentiation from osteoprogenitors present in the femoral and vertebral marrow cell populations. We also addressed whether IGFBP messenger RNA levels are regulated by thyroid hormone (T3) and dexamethasone (dex) treatment in femoral vs. vertebral marrow stromal cells in vitro, since steroid hormones play an important role in skeletal function. Northern blot analyses revealed that there are distinct skeletal site differences in the gene expression of IGFBPs. The vertebral marrow cultures express IGFBP‐2 through ‐6 mRNAs, with IGFBP‐2, IGFBP‐4, and IGFBP‐6 mRNAs predominating. The femoral marrow stromal cell cultures express only IGFBP‐4 and IGFBP‐6. Importantly, vertebral marrow cultures have much higher IGFBP mRNA steady‐state levels than femoral cultures for all the detected IGFBP transcripts. IGFBP‐1 is not detected in either femoral or vertebral cultures. In addition to a skeletal site difference, we show that T3 and dex regulate the expression of specific IGFBP mRNAs. T3 treatment also upregulates IGF‐I protein secretion by vertebral marrow stromal cell cultures. Interestingly, the type I receptor for IGF‐I was expressed equivalently in cultures from the two skeletal sites. These findings have important implications for the anatomical site specificities of hormonal responses that are noted in the skeleton. J. Cell. Biochem. 81:229–240, 2001.

Reconciling quantitative ultrasound of the calcaneus with X-ray-based measurements of the central skeleton.

Osteoporosis is frequently undiagnosed before fracture because of the lack of availability of instruments to quantitate bone mass. To evaluate the utility of quantitative ultrasound (QUS) of the calcaneus to diagnose osteoporosis, we determined bone mineral density (BMD) of the posterior‐arterior spine, total hip, and femoral neck by dual‐energy X‐ray absorptiometry (DXA) and QUS in 312 women aged 50 years and older. A risk factor assessment (simple calculated osteoporosis risk estimation [SCORE]) also was quantitated in all women. Ninety‐four of the 312 women were diagnosed as osteoporotic based on T scores ≤ −2.5 at the spine, total hip, and/or femoral neck. The sensitivity of the individual central sites for the diagnosis of osteoporosis was 49% at the spine (46 of 94 women), 32% at the total hip (30 of 94 women), and 81% at the femoral neck (76 of 94 women). At a QUS T score ≤ −1, the peripheral technique had a sensitivity of 62% and a specificity of 72%. Combining a QUS T score of ≤ −1 followed by a risk factor assessment of women with a QUS T score ≥ −0.99 using a cut point of 11 increased sensitivity to 81% (comparable with femoral neck DXA) but decreased specificity to 58%. If peripheral QUS measurements and risk factor assessment are the only tools employed before initiation of therapy, the benefits of increased ease of diagnosis will need to be balanced against potentially unnecessary treatment in some normal patients and lack of treatment in some osteoporotic patients.

Correlations Among Bone Mineral Density, Broadband Ultrasound Attenuation, Mechanical Indentation Testing, and Bone Orientation in Bovine Femoral Neck Samples

Abstract. Broadband ultrasound attenuation (BUA) of the calcaneus has been found to correlate with bone mineral density (BMD) of the femoral neck. The purpose of this study was to determine if a correlation exists among femoral neck BUA, femoral neck BMD, and incremental indent depth, a qualitative indicator of local mechanical bone strength, in bovine samples, and if this correlation is dependent upon orientation. For 12 of the bovine samples obtained, BUA was measured at the femoral neck and was followed by a BMD determination of the same area. A 19 mm diameter bicortical core containing the center of the area of interest was removed, transversely cut into 7 mm, thick disks, and tested for hardness by indent depth. For these tests, BMD was well correlated with BUA (R2= 0.85, P < 0.001). An inversely proportional relationship with a modest correlation was found between indent depth and BMD (R2= 0.59, P= 0.026), and indent depth and BUA (R2= 0.57, P= 0.031). In a second set of tests involving 15 different bovine samples, a bicortical core was removed from the femoral neck. A trabecular bone cube measuring 1.5 cm on a side was removed from the center of the core. BUA and BMD measurements were made along the anterior–posterior (AP), medial–lateral (ML), and cephalic–caudal (CC) aspects of the cube. The cubes were randomly separated into three groups, cut in half perpendicular to the axis of interest, and tested for hardness by indent depth. In these tests, no significant difference was found in BMD among the three orientations of the cubes scanned (P= 0.77). In contrast, the BUA along the ML orientation of the cube was significantly greater than that along the AP orientation (P < 0.05). No significant difference was found in the incremental indent depth measurements among cube orientations (P= 0.41). In the test involving only trabecular bone, a much higher correlation between BMD and incremental indent depth was found regardless of cube orientation (R2= 0.64, P < 0.001). The data indicate that BUA, but not BMD, is affected by trabecular orientation, and that BMD is negatively correlated with incremental indent depth.