Analysis of relationships between sex hormone dynamics and bone metabolism and changes in bone mass in surgically induced menopause

A 3-year follow-up study was performed of bone metabolism and bene changes induced by surgical menopause as a consequence of hysterectomy and oophorectomy (OVX) in 52 nonmenopausal women. We investigated 22 bone parameters and determined seven bone indices as indieators of bone mineral content by dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and microdensitometry (MD). The significant correlations between levels of sex hormones and/or bone parameters and bone indices demonstrated that marked sex-steroid deficiency after surgical menopause induced bone uncoupling during high bone turnover and subsequent rapid bone loss in the early period after OVX. Principal component analysis using correlation coefficients suggested a seven-loading-factor matrix composed of bone parameters and a two loading-factor matrix composed of bone indices. Two groups of parameters—estradiol and estriol, and androstenedione together, and luteinizing hormone and follicle-stimulating hormone together—indicated that the rate of bone loss was greater in the trabecular bone than in the cortical bone. Three other groups of parameters—urine calcium, urine hydroxyproline, and serum bone Gla-protein together; serum alkaline phosphatase, serum calcium, and 1,25-dihydroxy-cliolecalciferol [1,25(OH)₂D] together; and plasma tartrateresistant acid phosphatase—indicated that bone uncoupling, with a prevalence of resorption over formation of bone, was greater in trabecular bone than in cortical bone and also that the magnitude and rate of bone loss in the axial vertebrae surpassed those in the appendicular metacarpals after OVX. Two other groups of parameters, namely, trabecular bone mineral density (D_d) and bone mineral content (D_c), both measured by DXA, and bone mineral density (L₂, L₃), measured by QCT, together; and the cortical thickness index (MCI), cortical bone mineral density (GS/D), and the ratio of GSmin/max, measured by MD, indicated that the relative rates of bone reduction at the 3-year follow-up were greater in the axial vertebrae than in the appendicular metacarpals. Thus, bone change in the trabecular bone was associated with rapid loss during the early phase after OVX, whereas that in the cortical bone was slow during the late phase.     

Volumetric quantitative computed tomography of the proximal femur: relationships linking geometric and densitometric variables to bone strength. Role for compact bone

Introduction In assessing cervical fractures of the proximal femur, this in vitro quantitative computed tomography (QCT) study had three objectives: to compare QCT to dual-energy X-ray absorptiometry (DXA) for predicting the failure load of the proximal femur, to compare the contributions of density and geometry to bone failure load, and to compare the contributions of cortical and trabecular bone to bone failure load. A novel three-dimensional (3D) analysis tool [medical image analysis framework (MIAF-Femur)] was used to analyze QCT scans. Methods The proximal ends of 28 excised femurs were studied (1) using QCT to separately measure bone mineral density (BMD) and geometric variables of trabecular and cortical bone, (2) using mechanical tests to failure in a stance configuration, and (3) using DXA to measure BMD. The variables were described with mean, standard deviation, and range. Correlation matrix and multivariate linear models were computed. Results Among correlations, cortical thicknesses of the femoral neck were significantly correlated with femoral failure load, especially of the inferoanterior quadrant (r ²=0.41; p<0.001), as was cortical volume at the “extended neck“ (r ²=0.41; p<0.001). Femoral failure load variance was best explained by a combination of QCT variables. Combining densitometric and geometric variables measured by QCT explained 76% of femoral failure load variance compared with 69% with the DXA model. Geometric variables (measured by QCT) explained 43% of femoral failure load variance compared with 72% for densitometric variables (measured by QCT). A model including only trabecular variables explained 52% of femoral failure load variance compared with 59% for a model including only cortical variables. Conclusion The QCT-MIAF reported here provides analysis of both geometric and densitometric variables characterizing cortical and trabecular bone. Confirmation of our results in an independent sample would suggest that QCT may better explain failure load variance for cervical fracture than the gold standard DXA-provided BMD. This work was supported in part by grants from EU, contract number: QLK6-CT-2002-02440-3DQCT     

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial

Summary

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength.

Introduction

To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength.

Methods

In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated.

Results

Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p?<?0.01) and QCT (5.7%, p?<?0.0001). Between-treatment differences were significant for trabecular spine (p?=?0.0017) [non-parametric test], trabecular trochanter (10.7%, p?<?0.0001), total hip (10.8%, p?<?0.0001), and compressive strength indices at femoral neck (8.6%, p?=?0.0001), and trochanter (14.1%, p?<?0.0001).

Conclusions

Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.     

Evaluation by microdensitometry and dual energy X-ray absorptiometry of changes in bone metabolism after gastrectomy.

We used microdensitometry (MD) and dual energy X-ray absorptiometry (DXA) to evaluate impaired bone metabolism in 79 patients who had undergone gastrectomy. With MD, radiographs are simultaneously taken of the second metacarpal bone and an aluminum step-wedge, and the images were analyzed by computer. DXA was used to measure the bone mineral density of the second through fourth vertebrae and the estimated volumetric bone mineral density (EstVBMD) was assessed. Significant positive correlations were obtained between EstVBMD as determined by DXA and metacarpal index (MCI) (r = 0.413, P < 0.01), peak of the cortex (GSmax) (r = 0.362, P < 0.05), peak of the middle portion of the bone marrow (GSmin) (r = 0.412, P < 0.01), and metacarpal bone mineral density (mBMD) (r = 0.413, P < 0.01) as determined by MD. When EstVBMD was compared with MCI, GSmax, GSmin, and mBMD according to sex, age, type of operation, and interval after operation, generally similar trends were obtained. We conclude that the determination by MD of various indices of bone metabolism is useful in the diagnosis of osteopathy after gastrectomy.     

Effects of Menopause on Age-Dependent Bone Loss in the Axial and Appendicular Skeletons in Healthy Japanese Women

To determine the effects of menopause on bone loss in different parts of the skeleton, bone mineral density (BMD) values were measured longitudinally in 85 healthy women. BMD values included the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) and quantitative CT (QCT) and the distal and midradius measured by DXA obtained over 5 years. BMD at the calcaneus was measured using DXA for 3 years, and the BMD values of the distal metaphyses and diaphyses of radius and tibia were measured using peripheral QCT (pQCT) for 4 years. The subjects were 19 premenopausal, 17 perimenopausal, 12 early postmenopausal and 38 late postmenopausal women with the respective average ages of 39.1 ± 7.1 (SD), 51.9 ± 2.9, 55.8 ± 1.8 and 61.9 ± 3.9 years at the start of measurement. Average years since menopause were 1.4 ± 1.8, 3.3 ± 1.3 and 12.7 ± 5.3 years, respectively. In the perimenopausal group, the annual rate of bone loss for lumbar trabecular bone measured by QCT, and for the calcaneus, and metaphyseal trabecular bone at the radius and tibia by pQCT were higher than the respective values in the premenopausal group. These values in the late postmenopausal group became significantly lower compared with those in the perimenopausal group, coming down to the level of the premenopausal group. While the annual rates of bone loss at the tibial diaphysis in the perimenopausal group were also higher than those in the premenopausal group, the values at the radial diaphysis by DXA or pQCT did not differ significantly. The reductions in the annual rates of bone loss with the passage of time after menopause were not marked in these cortical bone dominated sites. These data indicated that the annual rates of bone loss at trabecular bone dominated sites were accelerated in both axial and appendicular skeletons. Diaphyseal cortical bone, however, seemed to be less sensitive to estrogen withdrawal. Other factors, such as genetics and calcium/vitamin D metabolism, would also affect the age-dependent bone loss at the cortical bone dominated sites after menopause. Received: 30 October 1998 / Accepted: 6 April 1999     

European semi-anthropomorphic spine phantom for the calibration of bone densitometers: Assessment of precision,stability and accuracy the European quantitation of osteoporosis study group

Up to now it has not been possible to reliably cross-calibrate dual-energy X-ray absorptiometry (DXA) densitometry equipment made by different manufacturers so that a measurement made on an individual subject can be expressed in the units used with a different type of machine. Manufacturers have adopted various procedures for edge detection and calibration, producing various normal ranges which are specific to each individual manufacturer's brand of machine. In this study we have used the recently described European Spine Phantom (ESP, prototype version), which contains three semi-anthropomorphic vertebrae of different densities made of simulated cortical and trabecular bone, to calibrate a range of DXA densitometers and quantitative computed tomography (QCT) equipment used in the measurement of trabecular bone density of the lumbar vertebrae. Three brands of QCT equipment and three brands of DXA equipment were assessed. Repeat measurements were made to assess machine stability. With the large majority of machines which proved stable, mean values were obtained for the measured low, medium and high density vertebrae respectively. In the case of the QCT equipment these means were for the trabecular bone density, and in the case of the DXA equipment for vertebral body bone density in the posteroanterior projection. All DXA machines overestimated the projected area of the vertebral bodies by incorporating variable amounts of transverse process. In general, the QCT equipment gave measured values which were close to the specified values for trabecular density, but there were substantial differences from the specified values in the results provided by the three DXA brands. For the QCT and Norland DXA machines (posteroanterior view), the relationships between specified densities and observed densities were found to be linear, whereas for the other DXA equipment (posteroanterior view), slightly curvilinear, exponential fits were found to be necessary to fit the plots of observed versus specified densities. From these plots, individual calibration equations were derived for each machine studied. For optimal cross-calibration, it was found to be necessary to use an individual calibration equation for each machine. This study has shown that it is possible to cross-calibrate DXA as well as QCT equipment for the measurement of axial bone density. This will be of considerable benefit for large-scale epidemiological studies as well as for multi-site clinical studies depending on bone densitometry.A Concerted Action of the European Community's COMAC-BME programme 1989–92. For further details of the Study Group see Appendix.     

定量CT对2型糖尿病性骨质疏松的诊断意义

2型糖尿病(type 2 diabetes mellitus, T2DM)通过多种因素影响骨微结构和骨密度,导致骨强度下降,骨折风险增加。定量CT(quantitative computed tomography, QCT)测定三维体积骨密度(volume bone mineral density, vBMD)优于双能X线吸收法(dual energy X-ray absorptiometry, DXA)测定的面积骨密度(area bone mineral density, aBMD)对T2DM患者骨折风险评估,还能发现松质骨的结构改变、皮质骨多孔性结构,对骨量细微改变具有高敏感性。将QCT与有限元分析法结合,通过骨密度、骨组织结构同时分析骨应力来评价骨强度,对T2DM患者骨折风险的预测更有价值。     

骨质疏松绵羊模型松质骨及皮质骨的微观结构及力学性能变化的研究

目的观察去势手术对绵羊皮质骨和松质骨的骨密度、骨小梁结构及力学性能的影响。方法20只雌性成年绵羊（4±1.5）随机分为去势4个月组（OVX-4months）（4只）、去势12个月组（OVX-12months）（8只）和假手术（Sham）组（8只）。OVX组行双侧卵巢切除术,假手术组仅显露双侧卵巢,术中测定腰椎骨密度。分别与术后4、12个月处死动物,测定股骨颈、股骨干及股骨髁的骨密度,并行MicroCT分析及生物力学测试。结果去势12个月后（OVX-12months）组腰椎、股骨颈及股骨髁的骨密度较对照组显著降低,而皮质骨骨密度无明显降低。其松质骨的相对骨体积（BV/TV）、骨小梁厚度（Tb.Th）、骨小梁数目（Tb.N）较对照组显著降低,表面积体积比（BS/BV）、骨小梁间隙（Tb.Sp）则较对照显著增高。生物力学测试表明,去势12个月后,腰椎松质骨的最大压缩应力分别较Sham组和OVX-12months组下降82.5%和85.9%,力学强度显著下降,而皮质骨的力学强度无显著变化。结论去势12个月后,绵羊腰椎、股骨部的松质骨BMD及骨小梁空间结构参数明显降低,力学强度也显著下降,可以作为骨质疏松的大动物模型。而皮质骨的骨密度和力学强度下降不明显,需要更长的去势时间。     

Quantitative computed tomography (QCT) of the forearm using general purpose spiral whole-body CT scanners: Accuracy,precision and comparison with dual-energy X-ray absorptiometry (DXA)

BackgroundDual-energy X-ray absorptiometry (DXA) allows clinically relevant measurement of bone mineral density (BMD) at central and appendicular skeletal sites, but DXA has a limited ability to assess bone geometry and cannot distinguish between the cortical and trabecular bone compartments. Quantitative computed tomography (QCT) can supplement DXA by enabling geometric and compartmental bone assessments. Whole-body spiral CT scanners are widely available and require only seconds per scan, in contrast to peripheral QCT scanners, which have restricted availability, limited spatial resolution, and require several minutes of scanning time.This study evaluated the accuracy and precision of whole-body spiral CT scanners for quantitatively assessing the distal radius, a common site of non-vertebral osteoporosis-related fractures, and compared the CT-measured densitometric values with those obtained from dual-energy-X-ray absorptiometry.Subjects and methodsA total of 161 postmenopausal women with baseline lumbar spine BMD T-scores between ? 1.0 and ? 2.5 underwent left forearm QCT using whole-body spiral CT scanners twice, 1 month apart. QCT volumes of interest were defined and analyzed at 3 specific radial regions: the ultradistal region by using slices at 8, 9, and 10 mm proximal to the ulnar styloid tip; the distal region by a slice 20 mm proximal; and the middle region by a slice 40 mm proximal. BMD, bone mineral content (BMC), volume, and average cortical thickness and circumference were measured. We evaluated QCT accuracy and precision and also report correlations between QCT and DXA for BMD and BMC.ResultsOverall accuracy and precision errors for BMD, BMC and volume were consistent with known skeletal QCT technology precision and were generally less than 3%. BMD and BMC assessed by QCT and DXA were correlated (r = 0.55 to 0.80).DiscussionWhole-body spiral CT scanners allow densitometric evaluations of the distal radius with good accuracy and very good precision. This original and convenient method provides a tool to further investigate cortical and trabecular bone variables in the peripheral skeleton in osteoporotic patients. These assessments, coupled with evaluation of the effects on cortical and trabecular bone measured in response to therapies for osteoporosis, may advance our understanding of the contributors to non-vertebral fracture occurrence.     

In vivo discrimination of hip fracture with quantitative computed tomography: Results from the prospective European Femur Fracture Study (EFFECT)

In assessing osteoporotic fractures of the proximal femur, the main objective of this in vivo case‐control study was to evaluate the performance of quantitative computed tomography (QCT) and a dedicated 3D image analysis tool [Medical Image Analysis Framework—Femur option (MIAF‐Femur)] in differentiating hip fracture and non–hip fracture subjects. One‐hundred and seven women were recruited in the study, 47 women (mean age 81.6 years) with low‐energy hip fractures and 60 female non–hip fracture control subjects (mean age 73.4 years). Bone mineral density (BMD) and geometric variables of cortical and trabecular bone in the femoral head and neck, trochanteric, and intertrochanteric regions and proximal shaft were assessed using QCT and MIAF‐Femur. Areal BMD (aBMD) was assessed using dual‐energy X‐ray absorptiometry (DXA) in 96 (37 hip fracture and 59 non–hip fracture subjects) of the 107 patients. Logistic regressions were computed to extract the best discriminates of hip fracture, and area under the receiver characteristic operating curve (AUC) was calculated. Three logistic models that discriminated the occurrence of hip fracture with QCT variables were obtained (AUC = 0.84). All three models combined one densitometric variable—a trabecular BMD (measured in the femoral head or in the trochanteric region)—and one geometric variable—a cortical thickness value (measured in the femoral neck or proximal shaft). The best discriminant using DXA variables was obtained with total femur aBMD (AUC = 0.80, p = .003). Results highlight a synergistic contribution of trabecular and cortical components in hip fracture risk and the utility of assessing QCT BMD of the femoral head for improved understanding and possible insights into prevention of hip fractures. © 2011 American Society for Bone and Mineral Research.     

Advanced CT based In Vivo Methods for the Assessment of Bone Density, Structure, and Strength

Based on spiral 3D tomography a large variety of applications have been developed during the last decade to asses bone mineral density, bone macro and micro structure, and bone strength. Quantitative computed tomography (QCT) using clinical whole body scanners provides separate assessment of trabecular, cortical, and subcortical bone mineral density (BMD) and content (BMC) principally in the spine and hip, although the distal forearm can also be assessed. Further bone macrostructure, for example bone geometry or cortical thickness can be quantified. Special high resolution peripheral CT (hr-pQCT) devices have been introduced to measure bone microstructure for example the trabecular architecture or cortical porosity at the distal forearm or tibia. 3D CT is also the basis for finite element analysis (FEA) to determine bone strength. QCT, hr-pQCT, and FEM are increasingly used in research as well as in clinical trials to complement areal BMD measurements obtained by the standard densitometric technique of dual x-ray absorptiometry (DXA). This review explains technical developments and demonstrates how QCT based techniques advanced our understanding of bone biology.     

Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight.

We measured cortical and trabecular bone loss using QCT of the spine and hip in 14 crewmembers making 4- to 6-month flights on the International Space Station. There was no compartment-specific loss of bone in the spine. Cortical bone mineral loss in the hip occurred primarily by endocortical thinning. INTRODUCTION: In an earlier study, areal BMD (aBMD) measurements by DXA showed that cosmonauts making flights of 4- to 12-month duration on the Soviet/Russian MIR spacecraft lost bone at an average rate of 1%/month from the spine and 1.5%/month from the hip. However, because DXA measurements represent the sum of the cortical and trabecular compartments, there is no direct information on how these bone envelopes are affected by spaceflight. MATERIALS AND METHODS: To address this, we performed a study of crewmembers (13 males and 1 female; age range, 40-55 years) on long-duration missions (4-6 months) on the International Space Station (ISS). We used DXA to obtain aBMD of the hip and spine and volumetric QCT (vQCT) to assess integral, cortical, and trabecular volumetric BMD (vBMD) in the hip and spine. In the heel, DXA was used to measure aBMD, and quantitative ultrasound (QUS) was used to measure speed of sound (SOS) and broadband ultrasound attenuation (BUA). RESULTS AND CONCLUSIONS: aBMD was lost at rates of 0.9%/month at the spine (p < 0.001) and 1.4-1.5%/month at the hip (p < 0.001). Spinal integral vBMD was lost at a rate of 0.9%/month (p < 0.001), and trabecular vBMD was lost at 0.7%/month (p < 0.05). In contrast to earlier reports, these changes were generalized across the vertebrae and not focused in the posterior elements. In the hip, integral, cortical, and trabecular vBMD was lost at rates of 1.2-1.5%/month (p < 0.0001), 0.4-0.5%/month (p < 0.01), and 2.2-2.7%/month (p < 0.001), respectively. The cortical bone loss in the hip occurred primarily by cortical thinning. Calcaneal aBMD measurements by DXA showed smaller mean losses (0.4%/month) than hip or spine measurements, with SOS and BUA showing no change. In summary, our results show that ISS crewmembers, on average, experience substantial loss of both trabecular and cortical bone in the hip and somewhat smaller losses in the spine. These results do not support the use of calcaneal aBMD or QUS measurements as surrogate measures to estimate changes in the central skeleton.     

Imaging Technologies for Assessment of Skeletal Health in Men

Conventional radiography can detect most fractures, evaluate their healing, and visualize characteristic skeletal abnormalities for some metabolic bone diseases. Dual-energy X-ray absorptiometry (DXA) is used to measure areal bone mineral density (BMD) in order to diagnose osteoporosis, estimate fracture risk, and monitor changes in BMD over time. Vertebral fracture assessment by DXA can diagnose vertebral fractures with less ionizing radiation, greater patient convenience, and lower cost than conventional radiography. Quantitative computed tomography (QCT) measures volumetric BMD separately in cortical and trabecular bone compartments. High resolution peripheral QCT and high resolution magnetic resonance imaging are noninvasive research tools that assess the microarchitecture of bone. The use of these technologies and others has been associated with special challenges in men compared with women, provided insights into differences in the pathogenesis of osteoporosis in men and women, and enhanced understanding of the mechanisms of action of osteoporosis treatments.     

T lymphocyte-deficient mice lose trabecular bone mass with ovariectomy.

We examined OVX-induced bone loss in three TLD mouse models. In TLD mice, OVX caused trabecular bone loss equivalent to that of WT. In contrast, cortical bone loss with OVX was variable. We conclude that T lymphocytes do not influence OVX-induced trabecular bone loss. INTRODUCTION: We examined ovariectomy (OVX)-induced bone loss in three T lymphocyte-deficient (TLD) mouse models: nude mice, recombination activating gene 2-deficient (RAG2 KO) mice, and T cell receptor alpha chain-deficient (TCRalpha KO) mice. MATERIALS AND METHODS: Bone mass was examined by DXA, microCT, and histomorphometry. We also examined the effect of OVX on T lymphocytes in the bone marrow and spleens of wildtype (WT) mice and on in vitro osteoclastogenesis and colony forming unit-granulocyte macrophage (CFU-GM) activity in the bone marrow of WT and nude mice. RESULTS: In WT mice, OVX did not alter T lymphocyte number in the bone marrow but did increase T lymphocytes in the spleen. Comparison of bone mass in nude, RAG2 KO, and TCRalpha KO mice with WT as measured by DXA showed decreased femoral bone mass in nude mice and increased vertebral bone mass in RAG2 KO mice. In TCRalpha KO mice, femoral, tibial, and vertebral bone mass were decreased. In vertebrae and long bones, bone loss with OVX was consistently present in WT mice but variably present in TLD mice as measured by DXA. In contrast, microCT and histomorphometry showed similar trabecular bone loss after OVX in all mice. However, femoral cortical bone loss occurred only in WT and RAG2 KO mice. OVX produced similar trabecular bone loss in WT and TCRalpha KO mice and also induced cortical bone loss in both. Histomorphometry showed that TRACP(+) area in bones was increased by OVX in femurs from both WT and nude mice as was in vitro osteoclast-like cell formation and CFU-GM activity. CONCLUSIONS: These results show that OVX caused similar trabecular bone loss in both WT and TLD mice. The ability of DXA and measurement of cortical bone loss to show OVX-induced effects on bone mass was variable. It seems that T lymphocytes are not critical for OVX-induced trabecular bone loss in these mouse models.     

Trabecular and integral bone density in adults with sickle cell disease.

Sickle cell disease (SCD) is a hereditary disorder of hemoglobin synthesis that can affect the skeletal system owing to accelerated hematopoiesis and/or bone infarction. Additionally, several studies have suggested that a low bone mass is associated with SCD, partly because of adverse effects on growth and development. The few previous studies of bone mineral density (BMD) in these patients have utilized dual-photon or dual-energy x-ray absorptiometric (DXA) techniques, which may have limited value in this population because it cannot correct for differences in bone size. We undertook a study of BMD in the forearm of patients with sickle cell disease using peripheral quantitative computed tomography (QCT), which provides a measure of volumetric bone density for the trabecular bone component as well as cortical and trabecular bone together. We studied 32 African-American SCD patients with no known history of bone infarction in the wrist, and compared them with data from healthy African-American volunteers. We found a 13% lower integral (cortical and trabecular) BMD in the SCD patients (p=0.001), but no difference in trabecular BMD (p=0.40 for males, 0.32 for females). We hypothesize that the maintenance of trabecular BMD in the wrist may be related to the persistence of metabolically active red marrow in this region in adults with SCD.     

A new vitamin D analog, 2MD, restores trabecular and cortical bone mass and strength in ovariectomized rats with established osteopenia.

An orally active, highly potent analog of 1alpha,25-dihydroxyvitamin D3, 2MD, restores trabecular and cortical bone mass and strength by stimulating periosteal bone formation and decreasing trabecular bone resorption in OVX rats with established osteopenia. INTRODUCTION: The purposes of this study were to determine the effects of long-term treatment with 2-methylene-19-nor-(20S)-1alpha,25(OH)2D3 (2MD) on restoring bone mass and bone strength in ovariectomized (OVX) rats with established osteopenia and 2MD effects on bone formation and bone resorption on trabecular and cortical bone surfaces. MATERIALS AND METHODS: Sprague-Dawley female rats were sham-operated (sham) or OVX at 4 months of age. Beginning at 8 weeks after OVX, OVX rats were orally dosed with 2MD at 0.5, 1, 2.5, 5, or 10 ng/kg/day for 16 weeks. Serum calcium was measured at 6, 13, and 16 weeks after treatment, and bone mass and structure, bone formation, bone resorption, and bone strength were determined at the end of the study. RESULTS: Serum calcium did not change significantly with 2MD at 0.5 or 1 ng/kg/day, whereas it significantly increased at 2.5, 5, or 10 ng/kg/day. 2MD significantly and dose-dependently increased total body BMD, total BMC, and stiffness of femoral shaft (FS), maximal load and stiffness of femoral neck, and toughness of the fifth lumbar vertebral body (L5) at all doses compared with OVX controls. In 2MD-treated OVX rats, there was a dose-dependent increase in total BMD and total BMC of the distal femoral metaphysis (DFM), trabecular bone volume of L3, ultimate strength and stiffness of L5, and maximal load of FS compared with OVX controls at dosages>or=1 ng/kg/day. At dosages>2.5 ng/kg/day, most of the bone mass and bone strength related parameters were significantly higher in 2MD-treated OVX rats compared with sham controls. Bone histomorphometric analysis of L3 showed dose-dependent decreases in osteoclast number and osteoclast surface on trabecular bone surface and a dose-dependent increase in periosteal bone formation associated with 2MD treatment. CONCLUSIONS: 2MD not only restored both trabecular and cortical bone mass but also added bone to the osteopenic OVX rats beyond that of sham controls by stimulating bone formation on the periosteal surface and decreasing bone resorption on the trabecular surface. 2MD increased bone mass and strength at doses that did not induced hypercalcemia.     

Effect of aging on trabecular and compact bone components of proximal and ultradistal radius

Bone densitometry has become a major tool for osteoporosis risk assessment. The traditional dual-energy X-ray absorptiometry (DXA) methods are able to evaluate the bone mineral content (BMC; mg/cm) and the areal density (BMD; mg/cm²), but only quantitative computed tomography (QCT) has the potential to measure the true volumetric bone density in the sense of mass per unit volume (mg/cm³). Peripheral QCT (pQCT) measurements were carried out at the non-dominant radius using a Stratec XCT 960 (Unitrem, Roma) in 241 postmenopausal and 29 premenopausal women. The sites of evaluation were both the ultradistal and the proximal radius. The technique used has a coefficient of variation of 2% and it allows separation of the bone section into trabecular and cortical bone on the basis of density threshold. Bone mass of radius, hip and spine was also evaluated by DXA procedures. The bone density data obtained by pQCT were significantly correlated with all DXA measurements. The correlation coefficients between their respective BMD values ranged from 0.48 to 0.75, but for the BMC values of the radius the correlation coefficients ranged from 0.82 to 0.93. The BMD values measured by DXA, but not by pQCT, were positively related with patient heights. All pQCT density measurements, including those obtained at the proximal radius and containing exclusively cortical bone, where negatively related with age and years since menopause. A partial volume effect, which is increasingly relevant the thinner are the bone cortices, might explain that. However, by applying increasing density thresholds, cortical bone density seems to decrease with age as a consequence of a gradual density diminution from the inner part of the bone cortex outwards. Trabecular bone density decreases with aging, but its overall mass does not change as a consequence of an age-related enlargement of trabecular area. Thus, the proportion of trabecular bone over total bone rises, and this might be relevant for our understanding of the age-related changes in bone turnover and rate of bone loss.     

Use of Quantitative Computed Tomography to Assess for Clinically-relevant Skeletal Effects of Prolonged Spaceflight on Astronaut Hips

Introduction: In 2010, experts in osteoporosis and bone densitometry were convened by the Space Life Sciences Directorate at NASA Johnson Space Center to identify a skeletal outcome in astronauts after spaceflight that would require a clinical response to address fracture risk. After reviewing astronaut data, experts expressed concern over discordant patterns in loss and recovery of bone mineral density (BMD) after spaceflight as monitored by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). The pilot study described herein demonstrates the use of QCT to evaluate absence of recovery in hip trabecular BMD by QCT as an indicator of a clinically actionable response. Methodology: QCT and DXA scans of both hips were performed on 10 astronauts: once preflight and twice postflight about 1 wk and 1 yr after return. If trabecular BMD had not returned to baseline (i.e., within QCT measurement error) in 1 or both hips 1 yr after flight, then another QCT hip scan was obtained at 2 yr after flight. Results: Areal BMD by DXA recovered in 9 of 10 astronauts at 1 yr postflight while incomplete recovery of trabecular BMD by QCT was evident in 5 of 10 astronauts and persisted in 4 of the 5 astronauts 2 yr postflight. Conclusion: As an adjunct to DXA, QCT is needed to detect changes to hip trabecular BMD after spaceflight and to confirm complete recovery. Incomplete recovery at 2 yr should trigger the need for further evaluation and possible intervention to mitigate premature fragility and fractures in astronauts following long-duration spaceflight.     

Mineral loss in cortical and trabecular bone during high-dose prednisone treatment

Summary To evaluate the effect of prednisone and triple treatment (sodium fluoride, calcium, and vitamin D) on trabecular and cortical bone serial bone mineral content (BMC) measurements were made at a metaphyseal (BMC_D) and diaphyseal (BMC_P) site on the forearm on 31 consecutive and previously bone-healthy patients scheduled for at least 24 weeks high-dose prednisone treatment. The patients were randomized into two further treatment groups: group I (n=16) received prednisone plus triple treatment and group II (n=15) received only prednisone. The two groups were similar with regard to age, sex, prednisone dose, and initial BMC. During 24 weeks treatment, BMC_D (partially representing trabecular bone) and BMC_P (mainly representing cortical bone) fell significantly and similarly, demonstrating that there is no preventive effect on bone mineral loss on the triple regimen. The BMC fall after 12 weeks was significantly more pronounced for metaphyseal (partially trabecular) than for diaphyseal (cortical) bone, whereas the values did not differ significantly after 24 weeks; this indicates a greater sensitivity to the hormone treatment of trabecular bone. In the entire group, the fall in BMC correlated positively with individual prednisone dose, significant at the diaphyseal site (r=0.39,P<0.05), but not at the metaphyseal site (r=0.31, P=0.08). It is concluded that corticosteroid-induced osteopenia is a diffuse bone disease which affects trabecular as well as cortical bone, suggesting that BMC measured on the forearm reflects changes in bone mineral at other locations.     

Vertebral cortical bone mass measurement by a new quantitative computer tomography method: Correlations with vertebral trabecular bone measurements

Summary Previous studies comparing axial and appendicular skeleton have shown that trabecular bone loss is greater than cortical bone loss. However, whether the same difference exists between the trabecular and the cortical compartments of the vertebral body remains to be determined. In this study, we used quantitative computer tomography (QCT) to simultaneously measure the cortical rim of the vertebral body as well as trabecular bone. In 99 Caucasian women (mean age 53.8±13.0 years, range 26–79 years) we found a significant correlation between cortical mineral content (BMC_c) and both single (SE) and dual energy (DE) trabecular mineral content (BMC_T) (r=0.62,P<0.0001 for both regressions). The cross-sectional rates of bone loss per year were 1.32%, 1.16%, and 0.59% for SE-BMC_T, DE-BMC_T, and BMC_C, respectively. BMC_C decreased at a rate that was 45–51% that of SE-BMC_T and DE-BMC_T, respectively. Our results indicate that (1) QCT may provide a useful means to selectively measure cortical density in vertebral bodies; (2) the decrease of cortical density over time in the spine appears to have been underestimated previously by extrapolation from appendicular bone measurements; (3) because measurements of the entire vertebral body (exclusive of the posterior elements) may provide information that is more representative of spine changes with age, a measurement that includes both areas might be more useful than one measuring only the trabecular region.