A stochastic analysis of iliac trabecular bone dynamics

Published normal histomorphometric data were used to derive distributions of thicknesses of trabecular plates and completed bone remodelling units (the basic multicellular unit carrying out bone remodelling, the BMU, when completed is termed a structural unit BSU). A stochastic model was set up to investigate the predictions of current BMU theory. Each of 100 trabecular "thicknesses" was drawn from the appropriate normal distribution using a pseudorandom number generator. Each day, each of its two surfaces when quiescent was assumed to have a 1:900 chance of initiating a remodelling cycle. Resorption (active, 12 days; reversal phase, 27 days) was followed by formation (94 +/- 35 days) and resulted in BMU balance when resorption depth was 36.8 +/- 9.2 micron. Fenestration (thickness less than 0) was assumed to lead to permanent loss of the trabecula. The original model unrealistically increased its mean trabecular thickness as thin trabeculae were lost. This was corrected by assuming that thin trabeculae had greater osteoblastic stimulation and a consequent tendency to thicken, perhaps due to higher mechanical loading. Over 20 years, 14% of trabeculae were lost when the BMU balance was exact and the distribution of trabecular thicknesses was unchanged. About one-half of fenestrations were due to deeper-than-average resorption cavities developing in thin trabeculae, and the remainder to coincident remodelling on both surfaces. A 10% fall in osteoblast lifespan resulted in an additional 36.7% loss of trabecular bone volume and mean trabecular thickness fell to 83.1 micron, compatible with Courpron's data. Simulating more rapid mechanisms of bone loss, approximately 50% of trabeculae could be lost after ten years by the arrest of bone formation; the doubling of resorption depth with unchanged bone formation; and a doubling in the rate of initiation of new BMUs with unchanged bone formation rate, all three followed by complete recovery of BMU balance after only two years. In each case, mean trabecular thickness fell only transiently but trabeculae continued to be lost after recovery. Prolonged osteoblast life span was the most likely explanation for the increased mean trabecular thicknesses and trabecular bone volumes seen in patients with osteoporosis, when treated with sodium fluoride plus calcium supplements or daily injections of parathyroid peptide hPTH 1-34.     

The relationship between spinal trabecular bone mineral content and iliac crest trabecular bone volume

Summary The relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume has been studied in 84 patients, 23 with primary osteoporosis, 19 with osteoporosis secondary to inflammatory bowel disease, and 42 with nonsteroid-treated rheumatoid arthritis. Spinal trabecular bone mineral density was measured in the first three lumbar vertebrae by quantitative computed tomography, and iliac crest trabecular bone volume was assessed histomorphometrically in sections from trans-iliac biopsies using computerized techniques. In all 84 patients, there was a significant positive correlation between the two measurements (r=0.60,P<0.001). However, when the three patient groups were analyzed separately, a significant correlation was found in the group with secondary osteoporosis (r=0.65,P<0.01) but not in the patients with primary osteoporosis (r=0.07) or rheumatoid arthritis (r=0.19). These results indicate that the relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume differs according to the underlying disease process, these differences possibly reflecting variations in skeletal patterns of bone loss in different types of osteoporosis.     

Histomorphometric study of trabecular channels in normal iliac bone

Summary Cancellous bone channels in the normal iliac crest have been studied histologically and by histomorphometry, and their biological role has been considered. Eighty percent of trabecular channels were typical osteons with the same structural and remodeling features as cortical osteons. The similarity of osteons in these two locations was corroborated by the comparability of morphometric features. The points of difference between osteons in the two types of bone were irregular configurations of trabecular osteons and marrow cells in the central canal in some. Since the number of trabecular osteons decreases with age, and since active trabecular resorption cavities were few in number, it is unlikely that additional osteons are formed in normal bone after the active modeling phase of bone growth. It is improbable that they make a significant contribution to bone remodeling since their number decreases with age, and since the available surface of trabecular channels for remodeling is extremely small. However, it is probable that they aid the intraosseous microcirculation and mineral exchange in thick trabecula and bifurcations, where they are mainly located. The demarcation curves at the 95% confidence interval, which suggest the normal range for numbers of channels, was calculated from the scatter diagram against bone area.     

Tetracycline double-labeling of iliac trabecular bone in 41 normal adults

Summary A histomorphometric evaluation of the iliac crest trabecular bone remodeling was performed after tetracycline double-labeling in 41 normal Danes (12 males and 29 females) aged 19 to 56 years. The fraction of formative (osteoid covered) and resorptive surfaces was unrelated to age but higher in males than in females (P<0.02 andP<0.05, respectively). The appositional rate (0.65±0.12 m/day) was unrelated to age and sex, whereas the fractional labeled surfaces were higher (P<0.01) in the males (0.18±0.08 m²/m²) than in the females (0.12±0.05 m²/m²), and among the females inversely related to age (R=–0.38,P<0.05). The bone formation rate at BMU level (0.50±0.20 m³/m²/day) was unrelated to sex, but among the females inversely related to age R=–0.49,P<0.01). The bone formation rate at tissue level was higher (P<0.02) in the males (0.13±0.07 m³/m²/day) than in the females (0.07±0.03 m³/m²/day) and among the females inversely correlated to age (R=–0.43,P<0.05). The age- and sex-dependent variations in the dynamic parameters underline the importance of a more elaborated normal material.     

Temporal variations in iliac trabecular bone formation in vertebral osteoporosis

Summary The histologic heterogeneity of osteoporosis relative to normal controls has attracted great interest. There has been controversy as to whether patients with high turnover osteoporosis may convert to a normal or low turnover form, and vice versa. We have studied 44 patients over 12 years by dynamic histomorphometry and⁸⁵Sr kinetics + calcium balance performed within 60 days in 20 patients (Group 1) and 75–808 days apart in the remainder (Group 2). In the first group, the histologic tissue level bone formation rate (BFR/BV or BFR/BS) was predictive of the⁸⁵Sr measurements of bone formation (r=0.66P<0.01). There was no statistically significant correlation in Group 2 and the regression coefficients were significantly different (P=0.01). Periodic regression was used to determine if seasonal changes were responsible for this loss of correlation; none was found that was of statistical significance. No systematic changes with time in bone formation were found in Group 2 during the period of observation; nor were consistent secular changes detected when the data for both groups were examined according to procedure data. In conclusion, bone formation may change with time in postmenopausal osteoporosis. Evidence that these changes are systematic was not found and this has implications for the design of treatment studies.     

Age-related changes in iliac crest trabecular microanatomic bone structure in man

Age-related changes in the microanatomic structure of human iliac crest trabecular bone have been investigated in biopsies from 90 subjects, using a new computerised method which automatically identifies and quantifies nodes, free ends and a number of topologically defined struts. In both sexes there was a significant age-related decrease in the number of nodes and of trabecular struts, corrected for section area. In females, there was also a significant age-related decrease in the node to free end ratio (P less than 0.001), and the combined node-to-node and node-to-loop strut length, expressed as a percentage of total strut length (P less than 0.001) and a significant increase in free end to free end strut length (P less than 0.001). In males, the only additional age-related change was a significant increase in the cortex to free end strut length (P less than 0.005). These results indicate that loss of trabeculae resulting in decreased interconnectedness of the normal trabecular bone structural pattern, plays an important role in age-related bone loss in females. Removal of trabeculae also occurs in males but in less prominent, implying that trabecular thinning makes a greater contribution to age-related bone loss in males.     

Measurement of total resorption surface in iliac crest trabecular bone in man

Total resorption surface has been measured under ordinary light and polarized light in trabecular iliac crest bone from 57 healthy subjects and 40 patients with privational or malabsorption metabolic bone disease. Results obtained with the two methods were similar, although values for total resorption surface measured under polarized light were usually lower than those obtained under ordinary light in both groups of subjects studied. This most likely reflects the greater accuracy in the microscopic identification of resorption surface under polarized light.     

Histomorphometry of iliac crest trabecular bone in adult male baboons in captivity

Summary Dat in the literature on bone histomorphometry in the baboon are scant. This study provides data from analysis of trabecular bone of the iliac crest of 16 adult male chacma baboons (Papio ursinus) in captivity. Five animals were young adults judging by the presence of growth cartilage in the iliac crest biopsy. Bone volume resembled that in humans, but trabeculae were thinner and more closely spaced. Bone turnover appeared somewhat lower than in humans. Coupling of resorption and formation was excellent as judged by cellular and kinetic variables; erosion surface was an unreliable indicator of ongoing coupling. The similarities between human and baboon trabecular bone make the baboon suited for the study of microstructure and bone turnover of trabecular bone with relevance to humans.     

Normative data for iliac bone histomorphometry in growing children

Many insights into normal and pathologic bone development can only be gained by bone histomorphometry. However, the use of this technique in pediatrics has so far been hampered by the lack of reference data. Therefore, we obtained transfixing iliac bone samples from 58 individuals between 1.5 and 22.9 years of age (25 male; tetracycline labeling performed in 48 subjects), who underwent surgery for reasons independent of abnormalities in bone development and metabolism. The results of histomorphometric analyses of cancellous parameters and cortical width are presented as means and standard deviations, as well as medians and ranges in five age groups. In addition, the original data are available from the authors. There were significant age-dependent increases in both cortical width and cancellous bone volume, the latter being due to an increase in trabecular thickness. Osteoid thickness did not vary significantly with age. Bone surface-based indicators of bone formation showed an age-dependent decline, reflecting similar changes in activation frequency. Mineral apposition rate decreased continuously with age. Parameters of bone resorption did not vary significantly between age groups. Paired biopsies from adjacent sites, obtained in eight subjects, were used to examine the reproducibility of histomorphometric parameters in children. The lowest coefficients of variation (<10%) were found for structural measures, as well as mineral apposition rate and wall thickness. The highest variability was found for cellular parameters. The availability of reference material will greatly facilitate the use of histomorphometry in pediatrics.     

Biomechanical competence of iliac crest trabecular bone in autosomal dominant osteopetrosis type I

Cylindrical horizontal iliac crest trabecular bone biopsies were obtained from 9 patients with autosomal dominant osteopetrosis type I and 18 normal controls of comparable age/sex match. Maximum compressive stress, maximum stiffness, energy absorption capacity and maximum strain were calculated from load-deformation curves after a compression test. Ash density of the bone samples was measured after incineration. The maximum compressive stress was significantly increased in the patient group (12.6 +/- 2.6 (SE) MPa vs. 3.3 +/- 0.4 MPa, p less than 0.01), as was the ash density (0.61 +/- 0.05 g/cm3 versus 0.27 +/- 0.02 g/cm3, p less than 0.01). After correction for ash density (normalized maximum stress) the strength of the trabecular bone samples was still significantly increased in the patients (19.7 +/- 6.4 MPa x cm3/g versus 12.0 +/- 1.2 MPa x cm3/g, p less than 0.01). The maximum stiffness and energy absorption capacity were higher in the patients (p less than 0.01), with a corresponding lower maximum strain value (p less than 0.05). The maximum compressive stress correlated closely to the maximum stiffness and energy absorption capacity in both patients and controls, whereas no correlation to maximum strain was found. The maximum compressive stress thus seems to be representative for the two other biomechanical parameters. No significant correlations between age and maximum compressive stress (R = 0.38), ash density (R = 0.08), or normalized maximum stress (R = 0.45) were observed in type I osteopetrosis, whereas significant age-dependent decreases in maximum compressive stress (R = -0.65, p less than 0.02) and in ash density (R = -0.57, p less than 0.02) were observed in normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ovariectomy on iliac trabecular bone in baboons (Papio anubis)

Summary Biopsies were collected from the left iliac crest of six adult female baboons, after which three of the animals were ovariectomized. Biopsies were collected from the right iliac crest six months later. Histomorphometric evaluation of the biopsies revealed consistent increases in fractional forming surface, appositional rate, and volume-based bone formation rate after ovariectomy. The data indicate that bone turnover is increased following ovariectomy in the baboon.     

The concentration of calcium and phosphorus in trabecular bone from the iliac crest

Summary The concentrations of calcium and phosphorus were determined in central parts of bone trabeculae in the human iliac crest by means of an energy dispersive microanalysis technique. Two age groups, each consisting of six suddenly diseased male subjects, were investigated. It was found that the concentrations of calcium and phosphorus did not differ between young and old men. The obtained mean values were fairly alike and determined to 40 and 17 weight %, respectively.     

Bone material properties in trabecular bone from human iliac crest biopsies after 3- and 5-year treatment with risedronate.

Long-term effects of risedronate on bone mineral maturity/crystallinity and collagen cross-link ratio in triple iliac crest biopsies of osteoporotic women were evaluated. In this double-blinded study, 3- and 5-year treatment with risedronate arrested the tissue aging encountered in untreated osteoporosis and in osteoporosis treated with other antiresorptives. This effect may be contributing to risedronate's antifracture efficacy. INTRODUCTION: Risedronate is widely used in the treatment of osteoporosis. It reduces bone turnover, increases BMD, and decreases fracture risk. To date, there are no data available on the long-term effects of risedronate on bone material properties in humans. MATERIALS AND METHODS: Osteoporotic women enrolled in the VERT-NA trial received either risedronate (5 mg/day, orally) or placebo for up to 5 years. All subjects received calcium. They also received vitamin D supplementation if deficient at baseline. Triple iliac crest biopsies were collected from a subset of these subjects at baseline, 3 years, and 5 years. Mineral maturity/crystallinity and collagen cross-link ratio was measured in these biopsies using Fourier transform infrared imaging. RESULTS: Patients that received placebo exhibited increased mineral maturity/crystallinity and collagen cross-link ratio after 3 and 5 years compared with baseline values. On the contrary, patients that received risedronate retained baseline values in both bone material indices throughout. A more spatially detailed analysis revealed that this was achieved mainly through beneficial effects on active bone-forming areas. Surprisingly, patients that received risedronate achieved premenopausal values at bone-forming areas in both indices after 5 years of treatment. CONCLUSION: Long-term treatment with risedronate affects bone material properties (mineral maturity/crystallinity and collagen cross-link ratio) and arrests the tissue aging apparent in untreated osteoporosis. These changes at the material level of the bone matrix may contribute to risedronate's rapid and sustained antifracture efficacy in osteoporotic patients.     

Estimation of the three-dimensional wall thickness of completed remodeling sites in iliac trabecular bone

The wall thickness of completed remodeling sites in trabecular bone was estimated in 25 normal individuals and 5 patients with arthrosis of the knee, using 7 μm sections of undecalcified iliac crest bone. A systematic sampling procedure which gives a surface referent estimate of the thickness was applied. The efficiency of the sampling design was optimized by means of a cost-variance analysis. The proposed method of sampling which eliminates a common bias in bone histomorphometry is recommended for determinations of wall thickness, osteoid thickness, lamellar thickness, and distance between fluorochrome markers in trabecular bone.The intraindividual distributions of three-dimensional wall thickness were reconstructed from the measurements of apparent width by an unfolding procedure based on the geometric probability density function pertaining to randomly sectioned plates. Distributions of true wall thickness for the young normal individuals were unimodal and resembled normal distributions. The three-dimensional mean wall thickness was 61.4 ± 4.4 μm (± SID). It was demonstrated that the conventionally applied stereological transformation, which calculates the three-dimensional mean wall thickness from the mean apparent width by multiplying the latter by π/4, underestimates the three-dimensional mean wall thickness. An improved transformation is illustrated and is recommended for estimating three-dimensional mean thickness of plates from two-dimensional measurements in trabecular bone.     

Reconstruction of the resorptive site in iliac trabecular bone: A kinetic model for bone resorption in 20 normal individuals

The variations with time in function and morphology at the resorptive site in normal iliac crest trabecular bone were reconstructed from tetracycline double-labeled iliac crest bone biopsies from 20 normal individuals.Resorption depths below osteoclasts, mononuclear cells, and preosteoblast-like cells were measured by counting the number of lamellae of known thickness eroded. Mean resorption depth below osteoclasts was 19.0 (±4.9) μm. Lacunae containing mononuclear cells were deeper (P < < 0.0001), with a mean resorption depth of 49.1 (±10.2) μm. The deepest lacunae were lacunae containing preosteoblast-like cells, with a mean resorption depth of 62.6 (±12.5) μm. This depth was significantly deeper (P < 0.001) than the resorption depth found below mononuclear cells.Median total resorption period was 48 days (31–68; 95% confidence interval). Median osteoclastic function period was 8 days (6–12), median mononuclear cell function period was 34 days (24–48), and median period where preosteoblast-like cells were present in lacunae before matrix synthesis started was 9 days (6–13). Distribution curves describing the occurrence of the three cell types in relation to resorption depth showed that osteoclasts occupied the more superior parts of the resorption lacunae, with mononuclear cells and preosteoblast-like cells situated in the deeper parts. The distribution curves support the hypothesis that osteoclasts precede mononuclear cells, which again precede preosteoblast-like cells. Based on this hypothesis, curves showing the variation in resorption depth with time were constructed in duplicate. Resorption rates were calculated for three periods. An initial osteoclastic resorption rate showed a median value of 3.8 μm/day (2.4–6.0), a mixed osteoclastic-mononuclear rate was found to be 1.3 μm/day (1.2–1.6), and the terminal mononuclear resorption rate was 0.7 μm/day (0.3–1.2). Median total resorption rate was 1.4 μm/day (1.2–1.7). No significant differences between the distributions of completed wall thickness and preosteoblast-like cell resorption depths could be demonstrated.     

Reduced wall thickness of completed remodeling sites in iliac trabecular bone following anticonvulsant therapy

The calcification rate and the completed wall thickness of remodeling sites in trabecular bone were estimated in undecalcified sections of tetracycline double-labeled iliac crest bone biopsies from 20 epileptic patients aged 19 to 50 years receiving long-term combined anticonvulsant therapy and 20 age- and sex-matched normal individuals. Surface distributions of thickness were obtained by a systematic equidistant sampling procedure and three-dimensional (3-D) values estimated from the two-dimensional (2-D) measurements by means of a stereologic transformation. The mean 3-D completed wall thickness was slightly reduced (P < 0.01) in the epileptic patients (58.9 μ as compared to 62.8 Am), while no statistically significant change in the mean 3-D calcification rate (0.62 μ/day as compared to 0.64 μ/day) was found. Surface distributions of wall thickness and calcification rate were unimodal and resembled normal distributions in patients as well as in controls. The estimated duration of the formation period at remodeling sites was almost 4 months for the normal individuals and insignificantly shorter for the epileptic patients. Double determinations after 2 to 3 month intervals revealed no significant intraobserver bias in the estimates of the wall thickness or the calcification rate.     

Correlation between the compressive strength of iliac and vertebral trabecular bone in normal individuals

Intrabone and interbone variations and age-related changes in vertical and horizontal trabecular bone compressive strength (CS) were evaluated for loadbearing (vertebral) and nonloadbearing (iliac crest) trabecular bone from 30 normal individuals, 17 females and 13 males, aged 15-87 years. All had died suddenly. The vertebral bodies of Th6, L1, and L3 and the right and left iliac crests were frozen at -20 degrees C immediately after removal. Cylindrical bone samples in the vertical and horizontal direction were taken from the frozen bone, and load-deformation curves were recorded by a materials testing machine. For all vertebral bodies, the vertical CS was much larger than the horizontal CS (P less than 0.01), whereas no significant difference was found for the iliac crests. The anisotropy expressed as an index of vertical to horizontal CS, therefore, was higher in the vertebrae than in the iliac crest. The anisotropy index (Al) increased with age in the vertebrae but not in the iliac crest (r = 0.56, P less than 0.01). Age related, almost identical decreases in CS were observed in the vertebrae (vertical direction) (r = 0.81, P less than 0.01) and in the iliac crest (horizontal direction) (r = -0.69, P less than 0.01). In spite of the pronounced differences in the architecture between the vertebral body and iliac trabecular bone, the vertical vertebral CS could be predicted from the horizontal iliac crest CS (r = 0.88, P less than 0.01, SEE = 0.9 MPa). The vertical iliac crest CS showed a less significant correlation to the average vertical vertebral CS (r = 0.53, P less than 0.05, SEE = 1.25 MPa).     

Direct and indirect measurements of osteoid seam width in human iliac crest trabecular bone

The osteoid thickness index, calculated from the relative osteoid volume and surface, has been compared with the mean osteoid seam width, measured directly, in iliac crest trabecular bone from 57 normal subjects and 33 patients with privational or malabsorption metabolic bone disease. In normal biopsies the osteoid thickness index overestimated mean osteoid seam width by a variable amount and the two variables were only weakly correlated (r = 0.32, P < 0.01). In patients with hyperosteoidosis there was a stronger correlation between the osteoid thickness index and the true mean seam width (r = 0.89, P < 0.001). Examination of the mean width of individual seams pooled from 15 randomly selected patients in each group revealed a skewed distribution with thin seams predominating, especially in normal biopsies. Median seam width was significantly lower than mean seam width in both groups studied.We conclude that osteoid thickness index is an inaccurate method of predicting the mean osteoid seam width, especially in biopsies with normal osteoid amount. Median values of osteoid seam width are more representative of average seam width, both in normal and abnormal biopsies.