Trabecular and endocortical bone remodeling in postmenopausal osteoporosis: Comparison with normal postmenopausal women

To assess the bone turnover abnormalities which characterize postmenopausal osteoporosis with vertebral fractures (PMOp), a transiliac bone biopsy was performed after double labeling of the mineralizing front with tetracycline in 50 untreated PMOp patients who were compared with 13 healthy age-matched volunteer females. The analysis of bone remodeling and structure parameters demonstrated that PMOp is a disease affecting both the cancellous and the endocortical envelopes and characterized by increased resorption and by a marked decrease in the osteoblastic apposition rate due to a reduced duration of bone formation. This induces a decrease in the width of both individual osteons and trabeculae. In PMOp, the wide spectrum of bone turnover as compared with the controls, associated with the typical bimodal distribution of cancellous osteoid perimeter, allowed us to identify two subsets, one with normal turnover (NT) and one with high turnover (HT) representing 30% of the cases. When compared to NT, HT was characterized by increased osteoclast number, lower bone volume, thinner osteons, increased formation at the tissue-level and markedly decreased duration of formation. In HT the marked decrease in the duration of activity of osteoblasts and the markedly increased number of osteoclasts induced a greater decrease in bone volume, despite the increase of bone formation at the tissue level. These subsets could not be distinguished by any clinical or biochemical parameter except for serum bone gla protein (osteocalcin) which was significantly higher (as a group) in HT than in NT. The underlying cause for these two subsets is unknown. We conclude that PMOp affects the cancellous and the endocortical bone. Bone loss results from a wide spectrum of bone turnover abnormalities, with two distinct subsets, one with normal turnover and one with high turnover.     

Surface curvatures of trabecular bone microarchitecture.

Microstructure of trabecular bone has been examined with a particular emphasis on surface curvatures in two-phase (trabecular and intertrabecular space- i.e., marrow space) structures. Three trabecular bone samples, quantified as "plate-like," "rod-like," and a mixture of these two structural elements according to the structure model index (SMI), were subjected to analysis based on (differential) geometry. A correspondence between the SMI and the mean curvature was found. A method to measure surface curvatures is proposed. The gaussian curvatures averaged over the surfaces for the three analyzed bone structures were all found to be negative, demonstrating their surfaces to be, on average, hyperbolic. In addition, the Euler-Poincaré characteristics and the genus, both characterizing topological features of bone connectivity, were estimated from integral gaussian curvature (Gauss-Bonnet theorem). The three bone microstructures were found to be topologically analogous to spheres with one to three handles.     

Evaluation of trabecular microarchitecture in nonosteoporotic postmenopausal women with and without fracture

This study compared microscopic magnetic resonance imaging (μMRI) parameters of trabecular microarchitecture between postmenopausal women with and without fracture who have normal or osteopenic bone mineral density (BMD) on dual-energy X-ray absorptiometry (DXA). It included 36 postmenopausal white women 50 years of age and older with normal or osteopenic BMD (T-scores better than -2.5 at the lumbar spine, proximal femur, and one-third radius on DXA). Eighteen women had a history of low-energy fracture, whereas 18 women had no history of fracture and served as an age, race, and ultradistal radius BMD-matched control group. A three-dimensional fast large-angle spin-echo (FLASE) sequence with 137 μm × 137 μm × 400 μm resolution was performed through the nondominant wrist of all 36 women using the same 1.5T scanner. The high-resolution images were used to measure trabecular bone volume fraction, trabecular thickness, surface-to-curve ratio, and erosion index. Wilcoxon signed-rank tests were used to compare differences in BMD and μMRI parameters between postmenopausal women with and without fracture. Post-menopausal women with fracture had significantly lower (p < 0.05) trabecular bone volume fraction and surface-to-curve ratio and significantly higher (p < 0.05) erosion index than postmenopausal women without fracture. There was no significant difference between postmenopausal women with and without fracture in trabecular thickness (p = 0.80) and BMD of the spine (p = 0.21), proximal femur (p = 0.19), one-third radius (p = 0.47), and ultradistal radius (p = 0.90). Postmenopausal women with normal or osteopenic BMD who had a history of low-energy fracture had significantly different (p < 0.05) μMRI parameters than an age, race, and ultradistal radius BMD-matched control group of postmenopausal women with no history of fracture. Our study suggests that μMRI can be used to identify individuals without a DXA-based diagnosis of osteoporosis who have impaired trabecular microarchitecture and thus a heretofore-unappreciated elevated fracture risk.     

Increases in BMD correlate with improvements in bone microarchitecture with teriparatide treatment in postmenopausal women with osteoporosis.

Increases in BMD are correlated with improvements in 2D and 3D trabecular microarchitecture indices with teriparatide treatment. Therefore, improvements in trabecular bone microarchitecture may be one of the mechanisms to explain how BMD increases improve bone strength during teriparatide treatment. INTRODUCTION: Bone strength is determined by BMD and other elements of bone quality, including bone microarchitecture. Teriparatide treatment increases BMD and improves both cortical and trabecular bone microarchitecture. Increases in lumbar spine (LS) BMD account for approximately 30-41% of the vertebral fracture risk reduction with teriparatide treatment. The relationship between increases in BMD and improvements in cortical and trabecular microarchitecture has not yet been studied. MATERIALS AND METHODS: The relationship between increases in BMD and improvements in cortical and trabecular microarchitecture after teriparatide treatment was assessed using data from a subset of patients who had areal BMD measurements and structural parameters from transiliac bone biopsies in the Fracture Prevention Trial. 2D histomorphometric and 3D microCT parameters were measured at baseline and 12 (n = 21) or 22 (n = 36) mo. LS BMD was assessed at baseline and 12 and 18 mo, and femoral neck (FN) BMD was measured at baseline and 12 mo. Pearson correlation was performed to assess the relationship between actual changes in BMD and actual changes in microarchitectural parameters. RESULTS: Changes in LS BMD at 12 mo were significantly correlated with improvements in trabecular bone structure at 22 mo: 2D bone volume (r = 0.45, p = 0.02), 2D mean wall thickness (r = 0.41, p = 0.03), 3D bone volume (r = 0.48, p = 0.006), 3D trabecular thickness (r = 0.44, p = 0.01), 3D trabecular separation (r = -0.37, p = 0.04), 3D structural model index (r = -0.54, p = 0.001), and 3D connectivity density (r = 0.41, p = 0.02). Changes in LS BMD at 18 mo had similar correlations with improvements in bone structure at 22 mo. Changes in FN BMD at 12 mo were significantly correlated with changes in 2D mean wall thickness (r = 0.56, p = 0.002), 3D bone volume (r = 0.51, p = 0.004), 3D trabecular thickness (r = 0.44, p = 0.01), 3D trabecular separation (r = -0.46, p = 0.01), and 3D structural model index (r = -0.55, p = 0.001). CONCLUSIONS: Increases in BMD are correlated with improvements in trabecular microarchitecture in iliac crest of patients with teriparatide treatment. Therefore, improvements in trabecular bone microarchitecture may be one of the mechanisms to explain how BMD increases improve bone strength during teriparatide treatment.     

Quantification of the roles of trabecular microarchitecture and trabecular type in determining the elastic modulus of human trabecular bone.

The roles of microarchitecture and types of trabeculae in determining elastic modulus of trabecular bone have been studied in microCT images of 29 trabecular bone samples by comparing their Young's moduli calculated by finite element analysis (FEA) with different trabecular type-specific reconstructions. The results suggest that trabecular plates play an essential role in determining elastic properties of trabecular bone. INTRODUCTION: Osteoporosis is an age-related disease characterized by low bone mass and architectural deterioration. Other than bone volume fraction (BV/TV), microarchitecture of bone is also believed to be important in governing mechanical properties of trabecular bone. We quantitatively examined the role of microarchitecture and relative contribution of trabecular types of individual trabecula in determining the elastic property of trabecular bone. MATERIALS AND METHODS: Twenty-nine human cadaveric trabecular bone samples were scanned at 21-mum resolution using a microCT system. Digital topological analysis (DTA) consisting of skeletonization and classification was combined with a trabecular type-specific reconstruction technique to extract the skeleton and identify topological type of trabeculae of the original trabecular bone image. Four different microCT-based finite element (FE) models were constructed for each specimen: (1) original full voxel; (2) skeletal voxel; (3) rod-reconstructed, preserving rod volume and plate skeleton; and (4) plate-reconstructed, preserving plate volume and rod skeleton. For each model, the elastic moduli were calculated under compression along each of three image-coordinate axis directions. Plate and rod tissue fractions directly measured from DTA-based topological classification were correlated with the elastic moduli computed from full voxel model. RESULTS: The elastic moduli of skeleton models were significantly correlated with those of full voxel models along all three coordinate axes (r(2) = 0.38 approximately 0.53). The rod-reconstructed model contained 21.3% of original bone mass and restored 1.5% of elastic moduli, whereas the plate-reconstructed model contained 90.3% of bone mass and restored 53.2% of elastic moduli. Plate tissue fraction showed a significantly positive correlation (r(2) = 0.49) with elastic modulus by a power law, whereas rod tissue fraction showed a significantly negative correlation (r(2) = 0.42). CONCLUSIONS: These results quantitatively show that the microarchitecture alone affects elastic moduli of trabecular bone and trabecular plates make a far greater contribution than rods to the bone's elastic behavior.     

A joined role of canopy and reversal cells in bone remodeling — Lessons from glucocorticoid-induced osteoporosis

Successful bone remodeling demands that osteoblasts restitute the bone removed by osteoclasts. In human cancellous bone, a pivotal role in this restitution is played by the canopies covering the bone remodeling surfaces, since disruption of canopies in multiple myeloma, postmenopausal- and glucocorticoid-induced osteoporosis is associated with the absence of progression of the remodeling cycle to bone formation, i.e. uncoupling. An emerging concept explaining this critical role of canopies is that they represent a reservoir of osteoprogenitors to be delivered to reversal surfaces. In postmenopausal osteoporosis, this concept is supported by the coincidence between the absence of canopies and scarcity of cells on reversal surfaces together with abortion of the remodeling cycle. Here we tested whether this concept holds true in glucocorticoid-induced osteoporosis. A histomorphometric analysis of iliac crest biopsies from patients exposed to long-term glucocorticoid treatment revealed a subpopulation of reversal surfaces corresponding to the characteristics of arrest found in postmenopausal osteoporosis. Importantly, these arrested reversal surfaces were devoid of canopy coverage in almost all biopsies, and their prevalence correlated with a deficiency in bone forming surfaces. Taken together with the other recent data, the functional link between canopies, reversal surface activity, and the extent of bone formation surface in postmenopausal- and glucocorticoid-induced osteoporosis, supports a model where bone restitution during remodeling demands recruitment of osteoprogenitors from the canopy onto reversal surfaces. These data suggest that securing the presence of functional local osteoprogenitors deserves attention in the search of strategies to prevent the bone loss that occurs during bone remodeling in pathological situations.     

The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime

Thirty-seven patients were randomized to receive intermittent cyclic etidronate (400 mg/day oral for 2 weeks, followed by 13 weeks off treatment) or an ADFR treatment (100 micrograms/day oral triiodothyronine for 7 days, followed by 400 mg/day etidronate for 2 weeks and 12 weeks off treatment). Supplemental calcium (120 mg/day) and vitamin D3 (400 IU/day) were given throughout the study period to all patients. Biochemical analyses, iliac-crest bone biopsies, and lumbar bone mineral content (BMC) measurements were performed before and during 60 weeks of treatment. Sixteen patients in the intermittent cyclic etidronate group and 15 in the ADFR group completed 60 weeks of treatment. Serum alkaline phosphatase decreased from 185 (43) (mean, (SD] to 144 (35) (p less than 0.001) and from 221 (69) to 156 (43) (p less than 0.002) during intermittent cyclic etidronate treatment and ADFR treatment, respectively, without any significant changes in renal hydroxyproline excretion. Final resorption depth, trabecular bone activation frequency, and bone formation rate decreased significantly from 51.5 (48.4/60.0) microns (median (25%/75% quartiles] to 44.0 (39.6/46.2) microns (p less than 0.04), from 0.30 (0.17/0.62) year-1 to 0.10 (0.02/0.19) year-1 (p less than 0.03) and from 0.035 (0.020/0.081) microns3/microns2/day to 0.015 (0.002/0.025) microns3/microns2/day, p less than 0.03 respectively, during intermittent cyclic etidronate treatment, but were unchanged during ADFR treatment. No significant changes in trabecular bone volume, bone balance per remodeling cycle, or BMC were noted in either treatment group; no evidence of osteomalacia was found. Intermittent cyclic etidronate treatment may be effective in preventing bone loss and in decreasing the risk of trabecular plate perforation, and thereby maintaining the integrity of bone architecture, in postmenopausal osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of alendronate on bone quality and remodeling in glucocorticoid-induced osteoporosis: a histomorphometric analysis of transiliac biopsies.

Effects of alendronate (ALN) on bone quality and turnover were assessed in 88 patients (52 women and 36 men aged 22-75 years) who received long-term oral glucocorticoid exposure. Patients were randomized to receive oral placebo or alendronate 2.5, 5, or 10 mg/day for 1 year and stratified according to the duration of their prior glucocorticoid treatment. Transiliac bone biopsies were obtained for qualitative and quantitative analysis after tetracycline double-labeling at the end of 1 year of treatment. As previously reported in glucocorticoid-induced osteoporosis, low cancellous bone volume and wall thickness were noted in the placebo group as compared with normal values. Alendronate treatment was not associated with any qualitative abnormalities. Quantitative comparisons among the four treatment groups were performed after adjustment for age, gender, and steroid exposure. Alendronate did not impair mineralization at any dose as assessed by mineralization rate. Osteoid thickness (O.Th) and volume (OV/BV) were significantly lower in alendronate-treated patients, irrespective of the dose (P = 0.0003 and 0.01, respectively, for O.Th and OV/BV); however, mineral apposition rate was not altered. As anticipated, significant decreases of mineralizing surfaces (76% pooled alendronate group; P = 0.006), activation frequency (-72%; P = 0.004), and bone formation rate (-71%; P = 0.005) were also noted with alendronate treatment. No significant difference was noted between the changes observed with each dose. Absence of tetracycline label in trabecular bone was noted in approximately 4% of biopsies in placebo and alendronate-treated groups. Trabecular bone volume, parameters of microarchitecture, and resorption did not differ significantly between groups. In conclusion, alendronate treatment in patients on glucocorticoids decreased the rate of bone turnover, but did not completely suppress bone remodeling and maintained normal mineralization at all alendronate doses studied. Alendronate treatment did not influence the osteoblastic activity, which is already low in glucocorticoid-induced osteoporosis.     

A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis

Thirty-seven patients with postmenopausal crush fracture osteoporosis were randomized to oral cyclic estrogen/gestagen (n = 20) or oral calcium (2000 mg elemental calcium per day) (n = 17). Fourteen in each group completed 1 year of treatment. Iliac crest bone biopsies were obtained after intravital double labeling with tetracycline before and after treatment in 10 patients on estrogen/gestagen and 11 patients on calcium. In the estrogen/gestagen group the activation frequency in trabecular bone decreased from 0.52 + 0.11 (SEM) year-1 to 0.27 + 0.08 year-1 (p less than 0.01). No significant changes were found in resorption or formation periods. The osteoid surfaces and the mineralizing surfaces decreased (p less than 0.05), whereas the decrease in eroded surfaces was insignificant. Furthermore, no significant changes were observed in final resorption depth, wall thickness or bone balance per remodeling cycle. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.002), whereas the lumbar bone mineral content (BMC) increased (p less than 0.01). In the calcium group the extent and thickness of osteoid surfaces decreased (p less than 0.05) without significant changes in activation frequency. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.02). No significant changes were observed in lumbar BMC or the other histomorphometric parameters. The study supports that the positive effect of estrogen/gestagen on BMC can be explained by a reduction in the activation frequency of new remodeling cycles leading to a decreased remodeling space and an increase in mean bone age. There is no evidence of a positive balance per remodeling cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: A three‐year study

The trabecular bone score (TBS) is an index of bone microarchitectural texture calculated from anteroposterior dual‐energy X‐ray absorptiometry (DXA) scans of the lumbar spine (LS) that predicts fracture risk, independent of bone mineral density (BMD). The aim of this study was to compare the effects of yearly intravenous zoledronate (ZOL) versus placebo (PLB) on LS BMD and TBS in postmenopausal women with osteoporosis. Changes in TBS were assessed in the subset of 107 patients recruited at the Department of Osteoporosis of the University Hospital of Berne, Switzerland, who were included in the HORIZON trial. All subjects received adequate calcium and vitamin D3. In these patients randomly assigned to either ZOL (n = 54) or PLB (n = 53) for 3 years, BMD was measured by DXA and TBS assessed by TBS iNsight (v1.9) at baseline and 6, 12, 24, and 36 months after treatment initiation. Baseline characteristics (mean ± SD) were similar between groups in terms of age, 76.8 ± 5.0 years; body mass index (BMI), 24.5 ± 3.6 kg/m²; TBS, 1.178 ± 0.1 but for LS T‐score (ZOL–2.9 ± 1.5 versus PLB–2.1 ± 1.5). Changes in LS BMD were significantly greater with ZOL than with PLB at all time points (p < 0.0001 for all), reaching +9.58% versus +1.38% at month 36. Change in TBS was significantly greater with ZOL than with PLB as of month 24, reaching +1.41 versus–0.49% at month 36; p = 0.031, respectively. LS BMD and TBS were weakly correlated (r = 0.20) and there were no correlations between changes in BMD and TBS from baseline at any visit. In postmenopausal women with osteoporosis, once‐yearly intravenous ZOL therapy significantly increased LS BMD relative to PLB over 3 years and TBS as of 2 years. © 2013 American Society for Bone and Mineral Research.     

Iliac trabecular bone formation predicts radial trabecular bone density changes in type 1 osteoporosis.

In 28 patients with idiopathic or postmenopausal type 1 (spinal crush fracture) osteoporosis, resorption indices and dynamic measurements of trabecular bone formation based on in vivo tetracycline labeling in 7.5 mm transiliac biopsies have been compared with trends in radial cortical and trabecular bone density measured with computed tomography. Positive correlations were observed between trabecular bone density trends in the radius and indices of bone formation in the ilium. These were improved when one of the two resorption indices was included with a formation index in bivariate regressions. Marked interindividual variations in radial bone density trends were also seen in cortical bone. These correlated poorly with trends in trabecular bone. Weak negative relationships between cortical bone trends and indices relating to bone formation and resorption were observed, but a positive association was seen with single-labeled surfaces on iliac trabeculae. If, as has been suggested, there are periodic variations in bone formation, the results suggest that axial and peripheral trabecular bone density trends are synchronized in osteoporosis, perhaps in response to systemic factors, such as circulating hormones.     

Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis.

Some studies have indicated that the risk of fragility fractures in men increases as bone mineral levels decrease, but there is an overlap in the bone mineral density (BMD) measurements between patients with or without fractures. Furthermore, it has been suggested that the biomechanical competence of trabecular bone is dependent not only on the absolute amount of bone present but also on the trabecular microarchitecture. In the present study, 108 men (mean age 52.1 years) with lumbar osteopenia (T score < -2.5) were recruited to examine the relationships between BMD, architectural changes in trabecular bone, and the presence of vertebral fractures. Lumbar BMD was assessed from L2 to L4 in the anteroposterior view with dual-energy X-ray absorptiometry. At the upper left femur, hip BMD was measured at the transcervical site. Spinal X-ray films were analyzed independently by two trained investigators, and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle, or posterior vertebral height. Transiliac bone biopsy specimens were obtained for all patients. Histomorphometric studies were performed on an image analyzer, and the following parameters were determined: trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), number (Tb.N), and separation (Tb.Sp), interconnectivity index (ICI), characterization of the trabecular network (node count and strut analysis), and star volume of the marrow spaces. Spinal radiographs evidenced at least one vertebral crush fracture in 62 patients (group II) and none in 46 patients (group I). After adjusting for age, body mass index, and BMD, there were no significant differences between the two groups in BV/TV, Tb.Th, or star volume. In contrast, the mean values of ICI, free end-to-free end struts (FF/TSL), and Tb.Sp were significantly higher, whereas Tb.N and node-to-node struts (NN/TSL) were lower in patients with at least one vertebral fracture. Logistic regression analysis showed that only ICI, FF/TSL, NN/TSL, and Tb.N were significant predictors of the presence of vertebral fracture: odds ratios for an alteration of 1 SD ranged from 1.7 (1.0-3.2) for NN/TSL to 3.2 (1.1-10.1) for ICI. Patients with at least three vertebral fractures (n = 23) were categorized as "multiple fractures." The results of logistic regression showed that spine BMD, BV/TV, and all architectural parameters were significant predictors of multiple vertebral fractures: odds ratios for an alteration of 1 SD ranged from 2.2 (1.1-4.6) for star volume to 3.7 (1.4-9.7) for ICI. These results strongly suggest that bone trabecular microarchitecture is a major and independent determinant of vertebral fractures in middle-aged men with osteopenia.     

A three-dimensional simulation of age-related remodeling in trabecular bone.

After peak bone mass has been reached, the bone remodeling process results in a decrease in bone mass and strength. The formation deficit, the deficit of bone formation compared with previous resorption, results in bone loss. Moreover, trabeculae disconnected by resorption cavities probably are not repaired. The contributions of these mechanisms to the total bone loss are unclear. To investigate these contributions and the concomitant changes in trabecular architecture and mechanical properties, we made a computer simulation model of bone remodeling using microcomputed tomography (micro-CT) scans of human vertebral trabecular bone specimens. Up to 50 years of physiological remodeling were simulated. Resorption cavities were created and refilled 3 months later. These cavities were not refilled completely, to simulate the formation deficit. Disconnected trabeculae were not repaired; loose fragments generated during the simulation were removed. Resorption depth, formation deficit, and remodeling space were based on biological data. The rate of bone loss varied between 0.3% and 1.1% per year. Stiffness anisotropy increased, and morphological anisotropy (mean intercept length [MIL]) was almost unaffected. Connectivity density increased or decreased, depending on the remodeling parameters. The formation deficit accounted for 69-95%, disconnected trabeculae for 1-21%, and loose fragments for 1-17% of the bone loss. Increasing formation deficit from 1.8% to 5.4% tripled bone loss but only doubled the decrease in stiffness. Increasing resorption depth from 28 to 56 microm slightly increased bone loss but drastically decreased stiffness. Decreasing the formation deficit helps to prevent bone loss, but reducing resorption depth is more effective in preventing loss of mechanical stiffness.     

Micro-CT and mechanical evaluation of subchondral trabecular bone structure between postmenopausal women with osteoarthritis and osteoporosis

Summary  

An inverse relationship between osteoarthritis and osteoporosis has been debated over years. The microstructure of the femoral heads from postmenopausal osteoarthritic and osteoporotic women was evaluated with micro-CT. Significant differences were observed in microstructural parameters between them. Different microstructure might relate to the opposite bone defects in osteoarthritis and osteoporosis.     

Ovariectomy and trabecular bone remodeling in the dog

Summary The early effects of ovariectomy (OX) on serum biochemistry and trabecular bone remodeling in the dog were investigated. Adult beagle dams were ovariectomized (n=8) or sham-ovariectomized (n=6) and followed for 6 months. All dogs received an iliac crest biopsy at the time of surgery to establish baseline remodeling data. A second contralateral biopsy was obtained at sacrifice. Serum osteocalcin became significantly elevated approximately 8 weeks following OX and remained elevated for the duration of the study. Histomorphometric analysis of serial transilial specimens showed that, at 6 months, OX had significantly increased the rate of bone remodeling in the ilium. Six months following OX in the dog, changes in serum biochemistry and trabecular bone remodeling in the ilium are consistent with those seen in postmenopausal women suffering from “high remodeling osteoporosis”.     

Fractal dimension of trabecular bone projection texture is related to three-dimensional microarchitecture.

The purpose of this work was to understand how fractal dimension of two-dimensional (2D) trabecular bone projection images could be related to three-dimensional (3D) trabecular bone properties such as porosity or connectivity. Two alteration processes were applied to trabecular bone images obtained by magnetic resonance imaging: a trabeculae dilation process and a trabeculae removal process. The trabeculae dilation process was applied from the 3D skeleton graph to the 3D initial structure with constant connectivity. The trabeculae removal process was applied from the initial structure to an altered structure having 99% of porosity, in which both porosity and connectivity were modified during this second process. Gray-level projection images of each of the altered structures were simply obtained by summation of voxels, and fractal dimension (Df) was calculated. Porosity (phi) and connectivity per unit volume (Cv) were calculated from the 3D structure. Significant relationships were found between Df, phi, and Cv. Df values increased when porosity increased (dilation and removal processes) and when connectivity decreased (only removal process). These variations were in accordance with all previous clinical studies, suggesting that fractal evaluation of trabecular bone projection has real meaning in terms of porosity and connectivity of the 3D architecture. Furthermore, there was a statistically significant linear dependence between Df and Cv when phi remained constant. Porosity is directly related to bone mineral density and fractal dimension can be easily evaluated in clinical routine. These two parameters could be associated to evaluate the connectivity of the structure.