Patient-specific microarchitecture of vertebral cancellous bone: a peripheral quantitative computed tomographic and histological study

This study directly compares peripheral quantitative computed tomography (pQCT) and histology for the assessment of 11 morphological parameters. Sixty-eight cylindrical cancellous bone samples were cored from the thoracic (T-9) thoracolumbar (T-12 or L-1), and lumbar (L-4) vertebral bodies of nine autopsy subjects (aged 44–88 years). Four transverse slices were acquired by pQCT from the bottom to the top of each cylinder. Slice thickness was 300 μm and pixel size was 70 × 70 μm. Thin sections (5 μm) were obtained at the same location in the samples, stained with Von Kossa, and photographed. Classical morphological parameters and strut analysis parameters were measured on all images (272 pQCT and 272 matched histological sections). Because of the partial volume effect and specific thresholding procedure, pQCT overestimated the absolute value of the bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) by a factor 2. The trabecular number (Tb.N), trabecular spacing (Tb.Sp), and total strut length (TSL) were correctly estimated. However, the direct correlation between pQCT and histology was excellent (r² > 0.85, p < 0.001) for BV/TV, Tb.N, Tb.Sp, TSL, and star surface. For Tb.Th, number of nodes, and number of free ends, the correlation was also good (r² > 0.6, p < 0.001). Using a random regression model, we also explored the ability of these parameters to add structural information to the readily available BV/TV or apparent density. The model identified significant (p < 0.001) differences between subjects. For a given BV/TV, some patients had more trabeculae (Tb.N) that were thinner (Tb.Th) and more disconnected (higher free ends and star). This was observed for both histology and pQCT morphometrical data. Our analysis demonstrates the capacity of both histology and pQCT to detect subjects with specific structural patterns in vertebral cancellous bone.     

Predicting human vertebral bone strength by vertebral static histomorphometry

The study investigates the relationship between static histomorphometry and bone strength of human lumbar vertebral bone. The ability of vertebral histomorphometry to predict vertebral bone strength was compared with that of vertebral densitometry, and also with histomorphometry and bone strength of iliac crest bone biopsies. The material comprised matched sets of second lumbar vertebrae, third lumbar vertebrae, and two iliac crest bone biopsies from each of 21 women (19--96 years) and 24 men (23--95 years). One of the iliac crest biopsies and 9-mm-thick mediolateral slices of half of each of the entire vertebral bodies (L-2) were used for histomorphometry. The other iliac crest biopsies and the L-3 were destructively tested by compression. High correlation was found between BV/TV or Tb.Sp and vertebral bone strength (absolute value of r = 0.86 in both cases). Addition of Tb.Th significantly improved the correlation between BV/TV and bone strength, and the addition of bone space star volume significantly improved the correlation between Tb.Sp and bone strength (from absolute value of r = 0.86 to absolute value of r = 0.89 in both cases). Bone structure (connectivity density) was not capable of improving the prediction of bone strength of the vertebral body. The correlations between BV/TV of L-2 and bone strength of L-3 were comparable with the correlation obtained by quantitative computed tomography (QCT), peripheral QCT (pQCT), and dual-energy X-ray absorptrometry (DEXA) of L-3 and bone strength of L-3. The iliac crest was found to have low predictive power of vertebral bone strength (iliac BV/TV: r = 0.62; iliac bone strength: r = 0.67). No gender-related differences were found in any of the relationships. It was shown that trabecular bone volume BV/TV and mean trabecular plate separation Tb.Sp are good predictors of vertebral bone strength. The ability of histomorphometry to predict vertebral bone strength was comparable to that of densitometry. Bone structure assessed by connectivity density did not improve the correlation between static histomorphometric measures and vertebral bone strength. No gender-related differences were found in any of the relationships. Neither static histomorphometry nor biomechanical testing of iliac crest bone biopsies is a good predictor of vertebral bone strength.     

Effect of slow-release sodium fluoride on cancellous bone histology and connectivity in osteoporosis

We have previously demonstrated that a treatment regimen of slow-release sodium fluoride (SRNaF) and continuous calcium citrate increases lumbar bone mass, improves cancellous bone material quality, and significantly reduces vertebral fracture rate in osteoporotic patients. In order to assess whether such treatment also improves trabecular structure, we quantitated cancellous bone connectivity before and following 2 years of therapy with SRNaF in 23 patients with osteoporosis and vertebral fractures. In addition, we performed bone histomorphometry on the same sections used for connectivity measurements. There was a significant increase in L2-L4 bone mineral density during therapy (0.827 ± 0.176 g/cm² SD to 0.872 ± 0.166, p = 0.0004). Significant histomorphometric changes were represented by increases in mineral apposition rate (0.6 ± 0.4μm/d to 1.1 ± 0.7, p = 0.0078) and adjusted apposition rate (0.4 ± 0.3 μm/d to 0.6 ± 0.4, p = 0.016). On the other hand, trabecular spacing significantly declined (from 1375 ± 878 μm to 1052 ± 541, p = 0.05). Two-dimensional quantitation of trabecular struts on iliac crest histological sections disclosed significant increases in mean node number per mm² of cancellous tissue area (0.22 ± 0.12 vs. 0.39 ± 0.27, p = 0.0077), the mean node to free-end ratio (0.23 ± 0.21 vs. 0.41 ± 0.46, p < 0.05), and in the mean node to node strut length per mm² of cancellous area (0.098 ± 0.101 vs. 0.212 ± 0.183, p < 0.01). There were no significant changes in any of the measurements associated with free-end number or free-end to free-end strut length. When patients were divided into those with severe and mild-modest spinal bone loss (based upon initial lumbar bone density) the significant changes in connectivity occurred in patients with mild-moderate bone loss, but not in those with severe bone loss, suggesting that fluoride's effect is in part dependent on the presence of a certain critical amount of bone. This finding in combination with the previously reported increases in bone mass and bone material quality may explain the significant reduction in vertebral fracture rate observed with this particular fluoride regimen.     

Relationships between bone structure in the iliac crest and bone structure and strength in the lumbar spine

The purpose of this study was to examine the relationship between histomorphometric variables of cancellous bone structure and ultimate compressive strength (UCS) in the second lumbar vertebra (L2) and to determine whether structural variables in the iliac crest are predictive of the same variables and of UCS in L2. At autopsy, 7.5 mm diameter cores were removed from the iliac crest and from L2 of 29 subjects who had died suddenly without bone disease. Cancellous bone volume (BV/TV, %) was significantly lower in L2 than in iliac crest due to lower trabecular number (Tb.N, per mm) and thickness (Tb.Th, µm). There were significant correlations between iliac crest and L2 for BV/TV, Tb.N and trabecular separation (Tb.Sp, µm), but not for Tb.Th. BV/TV was negatively correlated, and Tb.Sp was positively correlated with age at both sites. Tb.Th was not significantly correlated with age in the iliac crest, but a significant negative correlation was observed in L2. The UCS of vertebral cores was negatively correlated with age. BV/TV and Tb.Th in L2 were positively correlated with UCS in L2. Cortical width and BV/TV in iliac crest were positively correlated with UCS in L2. We conclude that: (1) cancellous bone volume in the iliac crest is higher than in the lumbar spine due to thicker, more closely spaced trabecular plates, (2) the changes in structural variables with age are generally similar in the iliac crest and lumbar vertebra, but trabecular thinning with age is more evident in the spine than in the ilium, and (3) the compressive strength of cancellous bone in the lumbar spine is correlated with histomorphometric variables of bone structure, as measured both in the lumbar spine and in the iliac crest.     

Peripheral Quantitative Computed Tomography of the Tibia: Pediatric Reference Values

Peripheral quantitative computed tomography (pQCT) has been used in a number of pediatric studies. Reference data for children are primarily limited to the radius. The purpose of this study was to establish normal reference ranges for pQCT measurements of the tibia for children. A cross-sectional sample of healthy, white, non-Hispanic children aged 5–18 years (n = 416; 197 boys) was measured at the distal tibia metaphysis and diaphysis by pQCT to assess trabecular and cortical bone, respectively. Differences were determined between and within genders by height for bone geometry, density, and strength. Height-specific normal ranges were calculated, and gender-specific centile curves were generated. A positive, linear relationship was found between tibia cortical bone geometry and strength parameters and height (r² ≥ 0.58, p < 0.001), with mean values greater for boys than girls (p ≤ 0.05). Trabecular volumetric bone mineral density values were relatively stable, but greater in boys than girls independent of height or age (p ≤ 0.01). The reference data for pQCT analyses of the tibia provide additional information on bone size, geometry, and strength in children. pQCT technology provides an additional tool for the evaluation of bone health in young subjects.     

Parathyroid hormone (1–34) increases vertebral bone mass, compressive strength, and quality in old rats

Human parathyroid hormone 1–34 (PITH) exerts an anabolic effect on bone in younger rats. The aim of the present study was to examine the effect of PTH on vertebral bone in 2-year-old male rats. The rats were treated with daily injections of 15 nmol/kg PTH or vehicle (V) for 56 days. Tetracycline and calcein were injected on day 15 and day 40 of the treatment period, respectively. The PTH treatment did not influence the body weights of the rats, the volumes of whole vertebra, or the vertebral body heights. However, the PTH treatment induced profound changes in the bone structure. Histomorphometric analyses of the vertebral bodies (L-6) revealed an approximate doubling of the cancellous bone volume after PTH treatment from 24.6 ± 1.3% to 54.9 ± 2.0% (p < 0.001) as well as a doubling of the trabecular thickness while the bone surface/bone volume decreased by 60%. PTH treatment also increased bone formation as indicated by an increase in mineral apposition rate (from 0.42 ± 0.01 to 0.89 ± 0.01 μm/day, p < 0.01), increased mineralizing surface (from 7.8 ± 1.4 to 43.8 ± 1.9%, p < 0.01) and an increase in both volume-related and surface-related bone formation rates (5 and 11 times, respectively). The biomechanical properties were analyzed using standardized bone specimens from the vertebral bodies of L-4 by applying cranial-caudal compression in a materials testing machine. The PTH treatment induced a substantial increase in the strength of the vertebral body: ultimate load increased by 66%, ultimate stiffness by 47%, and energy absorption by 98%. The increase in vertebral body strength was also evident after normalizing the parameters to the cross sectional area and the ash content of the vertebral body specimens. PTH treatment increased ultimate stress from 26 ± 3 to 44 ± 3 N per mm² (p < 0.01) and increased ultimate load normalized to ash content per mm specimen height from 59 ± 4 to 72 ± 4 N (mm/mg) (p < 0.05). The PTH treatment induced an increase in dry defatted bone density and ash density of both the vertebral body specimen (L-4) and the whole vertebra (L-5). In conclusion, PTH showed a remarkable ability to stimulate bone formation in the vertebral body of old rats. Furthermore, the biomechanical analysis revealed an enhanced compressive bone strength, even after correction for the increased bone mass, indicating an improved bone quality after the PTH treatment.     

Transforming growth factor β (TGF-β) levels in the conditioned media of human bone cells: relationship to donor age, bone volume, and concentration of TGF-β in human bone matrix in vivo

Transforming growth factor-β (TGF-β) is thought to play an important role in human bone remodeling. In the present study, we examined constitutive differences in TGF-β levels in primary bone cell cultures from the iliac crest of 112 women, aged 28–79 years. TGF-β1 was the major TGF-β isoform in the conditioned media, as determined by neutralizing TGF-β activity with specific antibodies against TGF-β1–3 in the mink lung cell bioassay, and by enzyme-linked immunoassay (ELISA). TGF-β1 levels in the conditioned media did not change with donor age. There was a lack of association between TGF-β levels in vitro and the concentration of matrix-associated TGF-β in vivo. TGF-β1 levels failed to be associated with the local trabecular bone volume in the complete study population (r = +0.15, p = 0.16, n = 89). A significant association between TGF-β1 levels and bone volume was present in premenopausal women (r = +0.39, p = 0.02, n = 33), but was largely accounted for by the two samples with the highest TGF-β concentrations. In conclusion, our data suggest that TGF-β1 is the major TGF-β isoform produced by human bone cells in vitro, and that the constitutive secretion of TGF-β by bone cells does not change with age. Whether constitutive differences in TGF-β secretion may be a determinant of human bone mass remains to be clarified in further studies.     

Low-megahertz ultrasonic properties of bovine cancellous bone

Ultrasound offers a noninvasive means to detect changes that occur to the density of cancellous bone as a result of degenerative diseases such as osteoporosis. Techniques based on the velocity and frequency dependence of attenuation of ultrasonic pulses propagated through cancellous bone have proven sensitive to bone density. Most previous studies have investigated these two parameters in the frequency range of 0.1–1.0 MHz. The present study had two goals. The first was to measure three ultrasonic parameters: longitudinal mode velocity; broadband ultrasonic attenuation (BUA); and apparent integrated backscatter (AIB), at higher frequencies using a broadband 2.25 MHz measurement system. The second goal was to assess the dependence of these parameters on bone density. Twenty-one specimens of cancellous bone acquired from the proximal end of four bovine tibiae were investigated in this study. The apparent density of the specimens (determined with the bone marrow removed and the specimens thoroughly dry) ranged between 0.3 and 0.9 g/cm³. Ultrasonic measurements were performed along three mutually perpendicular directions corresponding to the anteroposterior (AP), mediolateral (ML), and superoinferior (SI) axes of the tibia. A linear regression was used to analyze the results of these measurements as a function of apparent density. Velocity demonstrated a highly significant linear increase with density for all three directions (AP: p < 0.001; ML: p < 0.001; SI: p < 0.01). AIB decreased with density in all three directions; however, only the ML and SI directions demonstrated a significant linear correlation (AP: p = n.s.; ML: p < 0.05; SI: p < 0.05). In the frequency range 0.5–1.0 MHz, BUA exhibited a significant linear increase in the AP and ML directions, but not the SI direction (AP: p < 0.05; ML: p < 0.01; SI: p = n.s.). In contrast, in the frequency range 1.0–2.0 MHz, BUA exhibited a highly significant increase with density in the SI direction, but no significant change in the AP and ML directions (AP: p = n.s., ML: p = n.s., SI: p < 0.001).     

Interrelationships between bone microarchitecture and strength in ovariectomized monkeys treated with teriparatide.

Bone microarchitecture measured at the iliac crest at 6 mo was confirmed to be a reasonable surrogate for, and a predictor of, architecture and strength of the femoral neck and lumbar vertebra after 18 mo of teriparatide treatment. However, the data taken together showed the importance of cortical bone volume for vertebra to assess pharmacological effects on bone quality. INTRODUCTION: Improvements in bone architecture with teriparatide treatment are suggested to contribute to fracture risk reduction in osteoporotic patients. Teriparatide significantly improves microarchitecture in the iliac crest of humans by stimulating bone modeling and remodeling processes that differ dramatically from those induced by antiresorptives. The relationship between improvements of bone microarchitecture and improvements of bone strength with teriparatide treatment has not yet been fully studied. MATERIALS AND METHODS: Ovariectomized monkeys were administered vehicle (n = 20); teriparatide 1.0 microg/kg/d (n = 19); or teriparatide 5.0 microg/kg/d (n = 21) for 18 mo. Iliac crest biopsies were obtained at 6 and 15 mo after initiation of treatment. Animals were killed after 18 mo of treatment, and adjacent vertebrae or contralateral proximal femora were processed for biomechanical or histomorphometric analyses. Pearson correlation analyses were performed to assess the relationship between biomechanical and static histomorphometric parameters of lumbar vertebra, femoral neck, and iliac crest biopsies. RESULTS: Static histomorphometric parameters of the 6- and 15-mo biopsies were significantly correlated with the vertebral and femoral neck parameters obtained at 18 mo of teriparatide treatment. Iliac crest biopsy parameters at 6 and 15 mo also correlated with vertebral and femoral neck strength at 18 mo. Static histomorphometry of the lumbar vertebra and femoral neck at 18 mo also significantly correlated with strength at these sites. However, cortical bone volume of the lumbar vertebrae had the strongest correlation with vertebral and femoral neck strength (r = 0.74 and 0.71, respectively). CONCLUSIONS: Teriparatide dose dependently improved cortical and trabecular microarchitecture of vertebra and femoral neck, as well as trabecular microarchitecture of the iliac crest. Bone microarchitecture at all sites was significantly correlated with lumbar vertebra and femoral neck strength. Cortical bone volume of vertebra had the strongest correlation with vertebral and femoral neck strength. Therefore, structural improvement seemed to be part of the mechanism for improved strength observed with teriparatide treatment. Trabecular bone architecture of the iliac crest at 6 mo also correlated with vertebral and femoral neck strength, as did femoral neck (cortical and trabecular) histomorphometry and trabecular histomorphometry of vertebra after 18 mo of treatment. Because clinical assessment of cortical bone volume is not readily possible for vertebra noninvasively, these findings confirm the importance of iliac crest biopsies to monitor skeletal health and show that biopsies are a reasonable surrogate to assess spine and femoral neck structure and function.     

Predictive value of bone mineral density and morphology determined by peripheral quantitative computed tomography for cancellous bone strength of the proximal femur

Peripheral quantitative computed tomography (pQCT) is an established diagnostic method for assessment of bone mineral density in the diagnosis of osteoporosis. However, the capacity of structural parameters of cancellous bone measured by high-resolution computed tomography remains to be explored. In 33 patients, bone mineral density (BMD) of the proximal femur was measured in vitro by pQCT using cylindrical biopsies from the intertrochanteric region harvested before the implantation of an artificial hip joint. By digital image analysis of CT scans, parameters derived from histomorphometry describing the microarchitecture of cancellous bone were measured. The biopsies were also loaded to failure by an uniaxial compression test to determine the biomechanical parameters, Young's modulus, strength, and maximum energy absorption (E(max)). Strong correlations were found for BMD vs. mechanical parameters (r = 0.73 for Young's modulus, r = 0.82 for strength, and r = 0.79 for E(max); p < 0.001, n = 29). The morphological parameters, bone volume per trabecular volume (BV/TV), apparent trabecular thickness (app.Tb.Th), apparent trabecular separation (app.Tb.Sp), and trabecular number (Tb.N), correlated significantly with all mechanical parameters. The combination of morphological parameters with BMD in a multivariate regression model led to an overall, but only moderate, increase in R(2) in all cases. Our data confirm the high predictive value of BMD for the mechanical competence of cancellous bone of the intertrochanteric region. However, quantification of cancellous bone structure by image analysis of CT scans may provide additional qualitative information for the analysis of bone strength.     

A study of trabecular bones in ovariectomized goats with micro-computed tomography and peripheral quantitative computed tomography

Osteoporotic fractures occur most frequently in trabeculae-rich skeletal sites. The purpose of this study was to use a high-resolution micro-computed tomography (micro-CT) to investigate the changes in trabecular bone microarchitecture and to use a peripheral quantitative computed tomography (pQCT) to study changes in volumetric bone mineral density (BMD) in a large animal model resulted from ovariectomy (OVX). Ten adult goats were used for this study. The first iliac crest biopsy was harvested before OVX and served as baseline; the second biopsy was collected 6 months later from the opposite side for both pQCT and micro-CT measurements. Results showed that after 6 months of OVX, the BMD of the iliac crest biopsies decreased significantly by 16.3% (P < 0.05). The bone volume density (BV/TV), trabecular number (Tb.N), and connectivity density (Conn.D) measured with micro-CT decrease significantly after OVX, with an average decrease of 8.34%, 8.51%, and 18.52% (P < 0.05 each), respectively. The trabecular plate separation (Tb.Sp) was 8.26% (P < 0.05) greater than baseline after OVX. Significant correlations were found between the reduction of BMD and the decreases of BV/TV and Tb.N (r = 0.839 and 0.719, respectively; P< 0.001 both), as well as the increase of Tb.Sp (r = -0.758, P< 0.001) and SMI (r = -0.697, P< 0.001). In conclusion, this was the first experimental study in goat model to show that OVX-induced bone loss in goats was attributed by deterioration of trabecular microarchitecture.     

The predictive value of quantitative computed tomography for vertebral body compressive strength and ash density

Whole lumbar vertebral sections (L₂ and L₃) were obtained from 30 elderly individuals aged 43–95 years, mean 81 years (13 females, 17 males). None of the subjects had had malignant diseases. Quantitative computed tomography (QCT) was performed on an EMI 7070 scanner. One 8 mm slice parallel to the end-plates was obtained from the center of each vertebral body. The trabecular bone mass in each slice was outlined interactively by means of a tracer-ball. A CT-histogram was recorded inside this area, and average CT-values were expressed in Hounsfield Units (HU).

The whole vertebral body (L₂) was compressed in a materials testing machine. From the central part of L₃, vertical cylindrical pure trabecular bone specimens were obtained. The biomechanical competence of these specimens was also assessed by means of a materials testing machine. Finally, all bone specimens were incinerated for determination of apparent ash-density.

Highly significant positive correlations were found between average CT-values and (a) stress values of the trabecular bone (r = 0.81, p < 0.001) and (b) ash-density of the pure trabecular bone (r = 0.81, p < 0.001). Furthermore, a significant positive correlation was found between CT-values and (a) total vertebral body load (r = 0.72, p < 0.001), (b) total vertebral body stress (load/cross-sectional area) (r = 0.55, p < 0.001) and (c) ash-density of the whole vertebral body (r = 0.76, p < 0.001).

It is concluded that quantitative computed tomography gives valid predictions of both vertebral trabecular bone mass and mechanical competence. The predictive value for whole vertebral body load, stress and ash-density, although less marked, is still highly significant.     

Evaluation of vertebral volumetric vs. areal bone mineral density during growth

Bone mineral “density” (BMD) measured by dual-energy X-ray absorptiometry (DEXA) does not represent the volumetric density (grams per cubic centimeter), but rather the areal density (grams per square centimeter). This distinction is important during growth. The purpose of this study was to measure vertebral dimensions in cadavers of young pigtail macaques (Macaca nemestrina), and to derive equations to predict the volumetric bone density from noninvasive measurements. We measured the areal bone density by DEXA, vertebral volume by underwater weighing, mineral content by ashing, dimensions of lumbar vertebrae by calipers, and dimensions of vertebrae by radiography. Somatometric measurements of the female lumbar vertebral bodies showed that the shape changed during growth. The bone mineral content from the densitometer correlated significantly with the ash weight (r = 0.99, error 8.7%). The correlation coefficient between the volumetric bone mineral density and areal BMD measurement was significant (r = 0.68, p < 0.0001) with a 9.5% error; this improved significantly to 0.82 (7.2% error) when the BMD was divided by the vertebral depth from the radiograph. Areal BMD showed a strong correlation with age (r = 0.82, p < 0.0001), with an average increase of 7.4%/year. In contrast, volumetric mineral density showed a weak relationship with age (r = 0.43, p < 0.01), for an average increase of 1.5%/year. When studying bone mineral density during growth, the differences between volumetric and areal bone mineral density should be taken into consideration. (     

Sex differences in age-related loss of vertebral trabecular bone mass and structure—biomechanical consequences

Density, structure, and biomechanical competence of trabecular bone were analyzed on cylinders from the central part of the third lumbar vertebral body (L₃) from 91 normal individuals aged 15—91 years (48 males and 43 females). A significant and identical age-related decrease (p < 0.001) in bone density (apparent ash-density and trabecular bone volume) was found for both males and females. The structural analyses revealed a marked, age-related increase (p < 0.001) in the distance between the horizontal trabeculae in both sexes. In individuals older than 75 years, this increase was significantly higher for females than for males (p < 0.05). No other significant sex-related differences could be demonstrated in the age-related changes in the trabecular network. The biomechanical compression tests showed a significant and identical age-related decrease (p < 0.001) in stress-values in the vertical direction for both males and females. When horizontal cylinders were compressed, a steady decrease of bone strength was seen in males, while in females there was a tendency to a pronounced loss of bone strength around the age of 40–50 years. The present study demonstrated clearly a sex-related difference in the changes in vertebral trabecular architecture with age, with a higher tendency to perforation of the horizontal supporting struts in females than in males. The biomechanical consequences of this in these normal individuals were minor—but might be very marked in osteoporotic patients.     

Comparative study of iliac crest and subchondral femoral bone in osteoarthritic patients.

This is a study of trabecular bone changes in selected regions of the femoral head. Iliac crest bone from osteoarthritic (OA) and control groups is compared to the bone from regions in the femoral head. The regions are the subchondral principal compressive and tensile areas. These areas of highest and lowest stress undergo dramatic change with OA. The compressive region has total cartilage loss and eburnation. Bone histomorphometry was done on undecalcified tissue sections stained by the von Kossa silver method and counter-stained with haematoxylin and eosin. Iliac crest histomorphometry is similar for the OA and control groups. The femoral trabecular structure in the stress regions changes in opposing directions with OA. In the compressive region the structural variables (BV/TV and BS/TV) increase [corrected], and in the tensile region decrease. Femoral bone turnover indices (OV/TV, OS/BS, and ES/BS) are no different, but femoral bone structure is different from that of the iliac crest. In OA patients there is no significant increase in iliac crest trabecular bone volume. The iliac crest is not useful to assess the bony changes in femoral OA.     

Static histomorphometry of human iliac crest and vertebral trabecular bone: a comparative study.

We recently developed a new, rapid method for conducting static histomorphometry on large histologic sections. This method has now been applied on both iliac crest and lumbar vertebral bone to compare the age-related changes at these two skeletal sites and to investigate the correlation between the histomorphometric measures at the iliac crest and the vertebral body. The material comprised matched sets of unilateral transiliac crest bone biopsies and lumbar vertebral bodies (L-2) from 24 women (19-96 years) and 24 men (23-95 years) selected from a larger autopsy material. Three female subjects (80, 88, and 90 years) had a known vertebral fracture of L-2. The iliac crest biopsies and 9-mm-thick mediolateral slices of half the entire vertebral bodies were embedded in methylmetacrylate, stained with aniline blue, and scanned into a computer with a flatbed image scanner at a high resolution. With a custom-made computer program the following static histomorphometric measures were determined: trabecular bone volume; marrow and bone space star volume; node-strut analysis; trabecular bone pattern factor; trabecular thickness; trabecular number; trabecular separation; and anisotropy of bone and marrow phase. In addition, connectivity density was measured (ConnEulor method). The results showed that the age-related changes in the static histomorphometric measures are generally similar in the iliac crest and the vertebral body, and that these age-related changes are independent of gender. An exception, however, is connectivity density, where the age-related changes are similar for women and men in the vertebral body but significantly different in the iliac crest. Furthermore, the results showed that the histomorphometric measures were weakly intercorrelated between the iliac crest and the vertebral body, despite the generally similar pattern in age-related changes at these two skeletal sites. The highest correlation coefficient was found for trabecular separation (Tb.Sp; r = 0.63). Trabecular bone volume showed a correlation coefficient of r = 0.59. It is concluded that static histomorphometry performed on one skeletal site does not automatically predict static histomorphometric measures at another skeletal site. Therefore, it is recommended that static histomorphometry be performed at the skeletal site of interest-if at all possible.     

Cancellous bone microdamage in the proximal femur: influence of age and osteoarthritis on damage morphology and regional distribution

This study describes the in vivo distribution of cancellous bone microdamage in the proximal femur of an autopsy control sample. In addition, in vivo microdamage in the region medial to the greater trochanter of the proximal femur is compared between patients with severe osteoarthritis and controls. Taken at autopsy, the control group comprised normal right proximal femora that were then cut in the coronal plane with an Exakt saw (n = 12; aged 20–83 years). Cancellous bone samples were taken from the subchondral principal compressive region, the medial principal compressive region, and medial to the greater trochanter. A cancellous bone core biopsy was taken of the region medial to the greater trochanter (of the proximal femur) from patients with primary osteoarthritis undergoing total hip replacement surgery (n = 33; aged 37–85 years). Samples were embedded in resin, and in vivo microdamage identified in 70-μm-thick sections using the basic fuchsin en bloc staining technique. Microdamage was similar in all proximal femur sites in controls, except in the subchondral principal compressive region, where a significantly smaller crack length (μm) was identified (p < 0.05). In the region medial to the greater trochanter, osteoarthritic vs. control group comparisons showed that the crack density (#/mm²) and crack surface density (mm/mm²) were not significantly different, but crack length was significantly less (p < 0.03) and damage volume fraction was significantly increased for osteoarthritics (p < 0.005). The osteoarthritic and control data for crack density, and the osteoarthritic data for damage volume fraction, showed a nonlinear increase with age. Furthermore, crack length was not dependent on damage volume fraction or age for either the osteoarthritic or control group. This study identified differences in microdamage between osteoarthritic and autopsy control cases. We hypothesize that these results are consistent with the reported bone material property differences for osteoarthritis. In addition, the relatively uniform distribution of microdamage in the control group suggests that the principal components of the femoral cancellous bone network are equally exposed to deformations resulting in microdamage. Further study into the factors that influence the accumulation and skeletal distribution of microdamage is fundamental to understanding skeletal health.     

Differentiating between orchiectomized rats and controls using measurements of trabecular bone density: A comparison among DXA,Histomorphometry, and peripheral quantitative computerized tomography

In studies of rat bone metabolism, trabecular bone density should be measured. Three established methods of measuring trabecular bone include trabecular bone volume by histomorphometry (BV/TV%), trabecular bone density by peripheral quantitative computerized tomography (pQCT), and areal bone density of trabecular-rich regions by dual x-ray absorptiometry (DXA). We compared the ability of these three methods to discriminate between orchiectomized (orchidectomized) rats and controls. Sixteen male Sprague-Dawley rats (400–425 g) were orchiectomized, and 16 others were controls. In vivo spine bone mineral density (BMD) was measured at the beginning of the study and again after 11 weeks. Rats were sacrificed, and ex vivo BMDs of the right femur and tibia were measured by DXA, followed by trabecular bone density of the right proximal tibia by pQCT. BV/TV% of the left proximal tibia was measured by histomorphometry. Differences between groups were detected by all three methods, but both the magnitude of the difference between groups and the variance of the measurements was much greater for histomorphometry and pQCT than for DXA. Consequently, the statistical significance for the difference between groups was comparable for all three methods. Of the sites measured with DXA, the proximal tibia had the greatest statistical significance for the difference between groups. In summary, all three methods can demonstrate the effect of orchiectomy on trabecular bone. The large differences between groups seen by histomorphometry are also seen by pQCT but not by DXA. We conclude that trabecular bone density by pQCT may be a reasonable surrogate for measurements by histomorphometry.Portions of the data presented here were presented at the 16th Annual Meeting of the American Society for Bone and Mineral Research, Kansas City, Missouri, September 30-September 9–13, 1994.     

Lumbar vertebral body compressive strength evaluated by dual-energy X-ray absorptiometry, quantitative computed tomography, and ashing

Bone densitometry with DXA (dual energy X-ray absorptiometry) and QCT (quantitative computed tomography) techniques are used for in vivo assessment of bone strength and thereby prediction of fracture risk. However, only few in vitro studies have investigated and compared these techniques’ ability to determine vertebral compressive strength. The aim of the present study was to (1) assess the predictive value of DXA, QCT, and pQCT (peripheral QCT) for vertebral bone compressive strength assessed by mechanical testing; (2) describe both linear and power relationship between density and strength; and (3) evaluate whether gender-related differences in the above relations were present. The material comprised human lumbar vertebrae L3 from 51 women and 50 men (age range: 18 to 96 years). The study showed that both DXA and CT techniques (QCT and pQCT) have a high predictive value for vertebral strength. The DXA BMD had a high correlation with maximum compressive load (r² = 0.86). The QCT and pQCT had high correlations with maximum compressive stress (r² = 0.75 and r² = 0.86, respectively). The correlation between ash density of the biomechanically tested specimen and maximum compressive stress was r² = 0.88. There were no differences between linear and power fit in the degree of determination between density and strength. There was no gender-related difference in the relationship between volumetric density and maximum compressive stress. In conclusion, it was demonstrated that DXA, QCT, and pQCT are ex situ equally capable of predicting vertebral compressive strength with a degree of determination (r²) between 75% and 86%. No differences were found between linear and power analysis of the relationship between density and strength, and no difference was found in the density strength relationship between women and men.     

Bone properties as estimated by mineral density, ultrasound attenuation, and velocity

Quantitative ultrasound (QUS) analysis of bone has been suggested to have a level of performance equal to dual-energy X-ray absorptiometry (DXA) for the assessment of fracture risk. In this study, QUS and DXA measurements were conducted on bovine trabecular bone in vitro using commercially available clinical instruments. The samples were then mechanically tested to obtain Young’s modulus and ultimate strength. In addition, QUS and DXA parameters of the human calcaneus (n = 34) were measured in vivo. The measurements revealed a significant effect of bovine bone size on broadband ultrasound attenuation (BUA) and speed of sound (SOS) in vitro. By normalizing the DXA and QUS results with bone thickness we could systematically improve their ability to predict bone strength. However, in bovine trabecular bone, BUA showed no significant linear correlation with either bone mineral density (BMD), Young’s modulus, or ultimate strength. This finding may be typical of only high-density and low-porosity bovine bone. We significantly improved prediction of ultimate strength by combining density and ultrasound velocity results as compared with assessments of volumetric BMD_vol (p < 0.05) or SOS (p < 0.001) alone. However, the improvement was not significant if BMD_vol, instead of wet density, was used. Altogether, 88% of the variation in the ultimate strength of bovine bone could be explained by combined density and ultrasound velocity. In vivo, SOS showed a weak negative correlation with heel width (r = −0.350). The in vivo measurements also showed a close correlation for BUA with BMD in the human calcaneus. This suggests that BUA is more suitable for quantitative analysis of low-density trabecular bone.