Intervertebral disc degeneration can predispose to anterior vertebral fractures in the thoracolumbar spine.

Mechanical experiments on cadaveric thoracolumbar spine specimens showed that intervertebral disc degeneration was associated with reduced loading of the anterior vertebral body in upright postures. Reduced load bearing corresponded to locally reduced BMD and inferior trabecular architecture as measured by histomorphometry. Flexed postures concentrated loading on the weakened anterior vertebral body, leading to compressive failure at reduced load. INTRODUCTION: Osteoporotic fractures are usually attributed to age-related hormonal changes and inactivity. However, why should the anterior vertebral body be affected so often? We hypothesized that degenerative changes in the adjacent intervertebral discs can alter load bearing by the anterior vertebral body in a manner that makes it vulnerable to fracture. MATERIALS AND METHODS: Forty-one thoracolumbar spine "motion segments" (two vertebrae and the intervertebral disc) were obtained from cadavers 62-94 years of age. Specimens were loaded to simulate upright standing and flexed postures. A pressure transducer was used to measure the distribution of compressive "stress" inside the disc, and stress data were used to calculate how compressive loading was distributed between the anterior and posterior halves of the vertebral body and the neural arch. The compressive strength of each specimen was measured in flexed posture. Regional volumetric BMD and histomorphometric parameters were measured. RESULTS: In the upright posture, compressive load bearing by the neural arch increased with disc degeneration, averaging 63 +/- 22% (SD) of applied load in specimens with severely degenerated discs. In these specimens, the anterior half of the vertebral body resisted only 10 +/- 8%. The anterior third of the vertebral body had a 20% lower trabecular volume fraction, 16% fewer trabeculae, and 28% greater intertrabecular spacing compared with the posterior third (p < 0.001). In the flexed posture, flexion transferred 53-59% of compressive load bearing to the anterior half of the vertebral body, regardless of disc degeneration. Compressive strength measured in this posture was proportional to BMD in the anterior vertebral body (r2 = 0.51, p < 0.001) and inversely proportional to neural arch load bearing in the upright posture (r2 = 0.28, p < 0.001). CONCLUSIONS: Disc degeneration transfers compressive load bearing from the anterior vertebral body to the neural arch in upright postures, reducing BMD and trabecular architecture anteriorly. This predisposes to anterior fracture when the spine is flexed.     

Restoring geometric and loading alignment of the thoracic spine with a vertebral compression fracture: effects of balloon (bone tamp) inflation and spinal extension.

BACKGROUND CONTEXT: In patients with osteoporosis, changes in spinal alignment after a vertebral compression fracture (VCF) are believed to increase the risk of fracture of the adjacent vertebrae. The alterations in spinal biomechanics as a result of osteoporotic VCF and the effects of deformity correction on the loads in the adjacent vertebral bodies are not fully understood. PURPOSE: To measure 1) the effect of thoracic VCFs on kyphosis (geometric alignment) and the shift of the physiologic compressive load path (loading alignment), 2) the effect of fracture reduction by balloon (bone tamp) inflation in restoring normal geometric and loading alignment and 3) the effect of spinal extension alone on fracture reduction and restoration of normal geometric and loading alignment. STUDY DESIGN/SETTING: A biomechanical study using six fresh human thoracic specimens, each consisting of three adjacent vertebrae with all soft tissues and bony structures intact. METHODS: In order to reliably create fracture, cancellous bone in the middle vertebral body was disrupted by inflation of bone tamps. After removal of the bone tamps, the specimen was compressed using bilateral loading cables until a fracture was observed with anterior vertebral body height loss of >/=25%. Fracture reduction was performed under a compressive preload of 250 N first under the application of extension moments, and then using inflatable bone tamps. The vertebral body heights, kyphotic deformity of the fractured vertebra and adjacent segments and location of compressive load (cable) path in the fractured and adjacent vertebral bodies were measured on video-fluoroscopic images. RESULTS: The VCF caused anterior wall height loss of 37+/-15%, middle-height loss of 34+/-16%, segmental kyphosis increase of 14+/-7.0 degrees and vertebral kyphosis increase of 13+/-5.5 degrees (p<.05). The compressive load path shifted anteriorly by about 20% of anteroposterior end plate width in the fractured and adjacent vertebrae (p=.008). Bone tamp inflation restored the anterior wall height to 91+/-8.9%, middle-height to 91+/-14% and segmental kyphosis to within 5.6+/-5.9 degrees of prefracture values. The compressive load path returned posteriorly relative to the postfracture location in all three vertebrae (p=.004): the load path remained anterior to the prefracture location by about 9% to 11% of the anteroposterior end plate width. With application of extension moment (6.3+/-2.2 Nm) until segmental kyphosis and compressive load path were fully restored, anterior vertebral body heights were improved to 85+/-8.6% of prefracture values. However, the middle vertebral body height was not restored and vertebral kyphotic deformity remained significantly larger than the prefracture values (p<.05). CONCLUSIONS: The anterior shift of the compressive load path in vertebral bodies adjacent to VCF can induce additional flexion moments on these vertebrae. This eccentric loading may contribute to the increased risk of new fractures in osteoporotic vertebrae adjacent to an uncorrected VCF deformity. Bone tamp inflation under a physiologic preload significantly reduced the VCF deformity (anterior and middle vertebral body heights, segmental and vertebral kyphosis) and returned the compressive load path posteriorly, approaching the prefracture alignment. Application of extension moments also was effective in restoring the prefracture geometric and loading alignment of adjacent segments, but the middle height of the fractured vertebra and vertebral kyphotic deformity were not restored with spinal extension alone.     

Cortical and trabecular load sharing in the human vertebral body.

The biomechanical role of the vertebral cortical shell remains poorly understood. Using high-resolution finite element modeling of a cohort of elderly vertebrae, we found that the biomechanical role of the shell can be substantial and that the load sharing between the cortical and trabecular bone is complex. As a result, a more integrative measure of the trabecular and cortical bone should improve noninvasive assessment of fracture risk and treatments. INTRODUCTION: A fundamental but poorly understood issue in the assessment of both osteoporotic vertebral fracture risk and effects of treatment is the role of the trabecular bone and cortical shell in the load-carrying capacity of the vertebral body. MATERIALS AND METHODS: High-resolution microCT-based finite element models were developed for 13 elderly human vertebrae (age range: 54-87 years; 74.6 +/- 9.4 years), and parameter studies-with and without endplates-were performed to determine the role of the shell versus trabecular bone and the effect of model assumptions. RESULTS: Across vertebrae, whereas the average thickness of the cortical shell was only 0.38 +/- 0.06 mm, the shell mass fraction (shell mass/total bone mass)-not including the endplates-ranged from 0.21 to 0.39. The maximum load fraction taken by the shell varied from 0.38 to 0.54 across vertebrae and occurred at the narrowest section. The maximum load fraction taken by the trabecular bone varied from 0.76 to 0.89 across vertebrae and occurred near the endplates. Neither the maximum shell load fraction nor the maximum trabecular load fraction depended on any of the densitometric or morphologic properties of the vertebra, indicating the complex nature of the load sharing mechanism. The variation of the shell load-carrying capacity across vertebrae was significantly altered by the removal of endplates, although these models captured the overall trend within a vertebra. CONCLUSIONS: The biomechanical role of the thin cortical shell in the vertebral body can be substantial, being about 45% at the midtransverse section but as low as 15% close to the endplates. As a result of the complexity of load sharing, sampling of only midsection trabecular bone as a strength surrogate misses important biomechanical information. A more integrative approach that combines the structural role of both cortical and trabecular bone should improve noninvasive assessment of vertebral bone strength in vivo.     

Pull-out strength of Caspar cervical screws.

Anterior cervical instrumentation as an adjunct to bone fusion has an important role in cervical spine surgery. Posterior vertebral body cortex purchase is strongly recommended in the use of the Caspar system, although few biomechanical data exist to validate this requirement. In this study, Caspar screws were placed in 43 human cadaveric cervical vertebral bodies, either putting them into the posterior vertebral cortex as identified radiographically or penetrating it by 2 mm as recommended in the literature. Pull-out tests were conducted with tension applied to a connected plate at 0.25 mm/s, and force-deformation data were obtained. Failure typically occurred with clean pull-out; in most instances, cancellous bone remained attached to screw threads. Mean load without posterior cortical purchase was 375 +/- 53 N; with penetration it was 411 +/- 70 N. These differences were nonsignificant. Average deformation to failure was 1.41 +/- 0.10 mm in the group without posterior cortical penetration. In the posterior penetration group, mean deformation was 1.56 +/- 0.16 mm. Again, differences were not significant. Posterior cortical penetration does not improve the pull-out strength of Caspar screws in an isolated vertebral body model, but other biomechanical studies need to be done before insertion methods are altered.     

Independent and combined contributions of cancellous and cortical bone deficits to vertebral fracture risk in postmenopausal women.

Using iliac bone histomorphometry on 78 patients with vertebral fracture and 66 healthy postmenopausal women, cortical thickness discriminated at least as well as any cancellous bone structural index between the two groups. Subjects with a deficit in both cortical and cancellous bone had much greater likelihood of fracture. INTRODUCTION: Vertebral fracture is often attributed to disproportional loss of cancellous bone, but fracture patients may have deficits in cortical and cancellous bone. Accordingly, we examined the contribution of cortical and cancellous bone deficits, separately and together, to the likelihood of vertebral fracture. MATERIALS AND METHODS: Iliac bone histomorphometry was performed in 78 white woman with clinically apparent vertebral fracture, 66 healthy postmenopausal women, and 38 healthy premenopausal women. We measured cancellous bone volume (Cn.BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), cortical bone volume (Ct.BV/TV), and cortical thickness (Ct.Th). For each variable, a value of >1 SD below the mean in premenopausal women was treated as a putative risk factor, and its association with the presence or absence of fracture was determined by OR calculated by logistic regression and by receiver operating characteristic (ROC) curve analysis. Subsets of fracture and control subjects were separately matched for Cn.BV/TV and Ct.Th. RESULTS: All structural indices differed between fracture patients and controls except Ct.BV/TV. There was a weak but highly significant correlation between Cn.BV/TV and Ct.Th in the entire group (r = 0.389, r(2) = 0.151 p < 0.001). Many control subjects had a high value for one of these variables and a low value for the other. Ct.Th., Cn.BV/TV, and Tb.N were all significantly associated with vertebral fracture (ORs, 4.4-5.8; ROC area under the curve [AUC], 0.74-0.85). In subjects matched for Cn.BV/TV, Ct.Th was reduced by 29% (OR, 5.0), and in subjects matched for Ct.Th, Cn.BV/TV was reduced by 27% (OR, 5.0). In patients with deficits in both cortical and cancellous bone, the ORs ( 28-35 ) were much higher. CONCLUSIONS: Deficits in cortical bone (reduced value for Ct.Th) and in cancellous bone (reduced values for Cn.BV/TV or Tb.N) were equally effective in discriminating between subjects with and without vertebral fracture. With a deficit in both cortical and cancellous bone, the association with vertebral fracture was much stronger. Vertebral fracture is not the result of disproportionate loss of cancellous bone in the patients as a whole, although individual patients may have relatively greater deficits in either cancellous or cortical bone.     

Structural features and thickness of the vertebral cortex in the thoracolumbar spine

STUDY DESIGN: The thickness and structure of the vertebral body cortex were examined from sections of human cadaveric vertebrae. OBJECTIVES: The objectives were to identify the principal structural features of the cortex, to directly measure the minimum and maximum thicknesses of the cortex in the thoracolumbar spine, and to compare regional variations in the structure of the cortex. SUMMARY OF BACKGROUND DATA: The thickness of the vertebral cortical shell contributes to the compressive strength of the vertebral body. There is little consensus concerning the thickness and morphology of vertebral shell and endplate along the spine in existing data. METHODS: Human T1, T5, T9, L1, and L5 vertebral bodies (mean age 70.4 years) from 20 cadaveric spines were sectioned and photographed. The minimum and maximum cortical thickness of the shells and endplates in the midsagittal plane were measured from magnified images. RESULTS: The anterior shell thickness was significantly greater than the posterior shell and both endplates. Endplate thickness was greatest in the lower lumbar vertebrae. There was a significant decrease in cortex thickness over the central portion of endplates and shells, with a mean minimum thickness of 0.40 mm and a mean maximum thickness of 0.86 mm, with an overall mean of 0.64 +/- 0.41 mm. Increased porosity was also observed along the central regions of the cortical shells. In the lower thoracic and lumbar spine, a double-layered endplate structure was observed. CONCLUSIONS: Invasive techniques provide the only means to directly resolve the thickness and distribution of bone in the vertebral cortex. The cortex thickness and structure varies along the endplates and the anterior and posterior surfaces of the vertebral body. The implications of the so called double-layered endplate structure are unknown, but indicate the need for further study.     

Cancellous and cortical bone architecture and turnover at the iliac crest of postmenopausal osteoporotic women treated with parathyroid hormone 1-84

Treatment with parathyroid hormone [PTH(1-84)] increases lumbar spine bone mineral density and decreases vertebral fractures, but its effects on bone microarchitecture are unknown. We obtained iliac crest biopsies from postmenopausal osteoporotic women given placebo (n=8) or 100 microg PTH(1-84) for 18 (n=8) or 24 (n=7) months to assess cancellous and cortical bone formation and structure. At 18 months, cancellous bone volume (BV/TV) measured by microcomputed tomography and histomorphometry was 45-48% higher in subjects treated with PTH(1-84) versus placebo, a result of higher trabecular number (Tb.N) and thickness. The higher Tb.N appeared to result from intratrabecular tunneling. Connectivity density was higher and structure model index was lower, indicating a better connected and more plate-like trabecular architecture. Cancellous bone formation rate (BFR) was 2-fold higher in PTH(1-84)-treated subjects, primarily because of greater mineralizing surface. Osteoblast and osteoid surfaces were a nonsignificant 58% and 35%, respectively, higher with PTH(1-84) treatment. Osteoclast and eroded surface were unaffected by PTH(1-84). There were no effects of PTH(1-84) treatment on cortical thickness, or endocortical or periosteal BFR, but cortical porosity tended to be higher. Although cancellous BFR was lower at 24 than at 18 months, measures of cancellous and cortical bone structure were similar at both timepoints. The bone produced by PTH(1-84) had normal lamellar structure and mineralization with no abnormal histology. In conclusion, when compared with placebo, treatment of osteoporotic women with PTH(1-84) was associated with higher BV/TV and trabecular connectivity, with a more plate-like architecture, all consistent with the lower vertebral fracture incidence.     

Bone density, strength, and formation in adult cathepsin K (-/-) mice

Cathepsin K (CatK) is a cysteine protease expressed predominantly in osteoclasts, that plays a prominent role in degrading Type I collagen. Growing CatK null mice have osteopetrosis associated with a reduced ability to degrade bone matrix. Bone strength and histomorphometric endpoints in young adult CatK null mice aged more than 10 weeks have not been studied. The purpose of this paper is to describe bone mass, strength, resorption, and formation in young adult CatK null mice. In male and female wild-type (WT), heterozygous, and homozygous CatK null mice (total N=50) aged 19 weeks, in-life double fluorochrome labeling was performed. Right femurs and lumbar vertebral bodies 1-3 (LV) were evaluated by dual-energy X-ray absorptiometry (DXA) for bone mineral content (BMC) and bone mineral density (BMD). The trabecular region of the femur and the cortical region of the tibia were evaluated by histomorphometry. The left femur and sixth lumbar vertebral body were tested biomechanically. CatK (-/-) mice show higher BMD at the central and distal femur. Central femur ultimate load was positively influenced by genotype, and was positively correlated with both cortical area and BMC. Lumbar vertebral body ultimate load was also positively correlated to BMC. Genotype did not influence the relationship of ultimate load to BMC in either the central femur or vertebral body. CatK (-/-) mice had less lamellar cortical bone than WT mice. Higher bone volume, trabecular thickness, and trabecular number were observed at the distal femur in CatK (-/-) mice. Smaller marrow cavities were also present at the central femur of CatK (-/-) mice. CatK (-/-) mice exhibited greater trabecular mineralizing surface, associated with normal volume-based formation of trabecular bone. Adult CatK (-/-) mice have higher bone mass in both cortical and cancellous regions than WT mice. Though no direct measures of bone resorption rate were made, the higher cortical bone quantity is associated with a smaller marrow cavity and increased retention of non-lamellar bone, signs of decreased endocortical resorption. The relationship of bone strength to BMC does not differ with genotype, indicating the presence of bone tissue of normal quality in the absence of CatK.     

Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures

Postmenopausal women with vertebral fractures have abnormal bone microarchitecture at the distal radius and tibia by HR-pQCT, independent of areal BMD. However, whether trabecular plate and rod microarchitecture is altered in women with vertebral fractures is unknown. This study aims to characterize the abnormalities of trabecular plate and rod microarchitecture, cortex, and bone stiffness in postmenopausal women with vertebral fractures. HR-pQCT images of distal radius and tibia were acquired from 45 women with vertebral fractures and 45 control subjects without fractures. Trabecular and cortical compartments were separated by an automatic segmentation algorithm and subjected to individual trabecula segmentation (ITS) analysis for measuring trabecular plate and rod morphology and cortical bone evaluation for measuring cortical thickness and porosity, respectively. Whole bone and trabecular bone stiffness were estimated by finite element analysis. Fracture and control subjects did not differ according to age, race, body mass index, osteoporosis risk factors, or medication use. Women with vertebral fractures had thinner cortices, and larger trabecular area compared to the control group. By ITS analysis, fracture subjects had fewer trabecular plates, less axially aligned trabeculae and less trabecular connectivity at both the radius and the tibia. Fewer trabecular rods were observed at the radius. Whole bone stiffness and trabecular bone stiffness were 18% and 22% lower in women with vertebral fractures at the radius, and 19% and 16% lower at the tibia, compared with controls. The estimated failure load of the radius and tibia were also reduced in the fracture subjects by 13% and 14%, respectively. In summary, postmenopausal women with vertebral fractures had both trabecular and cortical microstructural deterioration at the peripheral skeleton, with a preferential loss of trabecular plates and cortical thinning. These microstructural deficits translated into lower whole bone and trabecular bone stiffness at the radius and tibia. Our results suggest that abnormalities in trabecular plate and rod microstructure may be important mechanisms of vertebral fracture in postmenopausal women.     

Locations of bone tissue at high risk of initial failure during compressive loading of the human vertebral body

Knowledge of the location of initial regions of failure within the vertebra - cortical shell, cortical endplates vs. trabecular bone, as well as anatomic location--may lead to improved understanding of the mechanisms of aging, disease and treatment. The overall objective of this study was to identify the location of the bone tissue at highest risk of initial failure within the vertebral body when subjected to compressive loading. Toward this end, micro-CT-based 60-micron voxel-sized, linearly elastic, finite element models of a cohort of thirteen elderly (age range: 54-87 years, 75+/-9 years) female whole vertebrae without posterior elements were virtually loaded in compression through a simulated disc. All bone tissues within each vertebra having either the maximum or minimum principal strain beyond its 90th percentile were defined as the tissue at highest risk of initial failure within that particular vertebral body. Our results showed that such high-risk tissue first occurred in the trabecular bone and that the largest proportion of the high-risk tissue also occurred in the trabecular bone. The amount of high-risk tissue was significantly greater in and adjacent to the cortical endplates than in the mid-transverse region. The amount of high-risk tissue in the cortical endplates was comparable to or greater than that in the cortical shell regardless of the assumed Poisson's ratio of the simulated disc. Our results provide new insight into the micromechanics of failure of trabecular and cortical bone within the human vertebra, and taken together, suggest that, during strenuous compressive loading of the vertebra, the tissue near and including the endplates is at the highest risk of initial failure.     

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

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

Differential effects of glucocorticoids on cortical appendicular and cortical vertebral bone mineral content

Summary The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval-36.0% to-8.1%) and cortical (-24.8%, 95% confidence interval-39.3% to-10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval-27.1% to-4.2%), but not the diaphyseal (-3.9%, 95% confidence interval-14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis.     

Contribution of Trabecular and Cortical Components to Biomechanical Behavior of Human Vertebrae: An Ex Vivo Study

Whereas there is clear evidence for a strong influence of bone quantity (i.e., bone mass or bone mineral density) on vertebral mechanical behavior, there are fewer data addressing the relative influence of cortical and trabecular bone microarchitecture. The aim of this study was to determine the relative contributions of bone mass, trabecular microarchitecture, and cortical thickness and curvature to the mechanical behavior of human lumbar vertebrae. Thirty‐one L3 vertebrae (16 men, 15 women, aged 75 ± 10 years and 76 ± 10 years, respectively) were obtained. Bone mineral density (BMD) of the vertebral body was assessed by lateral dual energy X‐ray absorptiometry (DXA), and 3D trabecular microarchitecture and anterior cortical thickness and curvature was assessed by micro‐computed tomography (µCT). Then compressive stiffness, work to failure, and failure load were measured on the whole vertebral body. BMD was correlated with compressive stiffness (r = 0.60), failure load (r = 0.70), and work to failure (r = 0.55). Except for the degree of anisotropy, all trabecular and cortical parameters were correlated with mechanical behavior (r = 0.36 to 0.58, p = .05 to .001, and r = 0.36 to 0.61, p = .05 to .0001, respectively). Stepwise and multiple regression analyses indicated that the best predictor of (1) failure load was the combination of BMD, structural model index (SMI), and trabecular thickness (Tb.Th) (R = 0.80), (2) stiffness was the combination of BMD, Tb.Th, and curvature of the anterior cortex (R = 0.82), and (3) work to failure was the combination of anterior cortical thickness and BMD (R = 0.68). Our data imply that measurements of cortical thickness and curvature may enhance prediction of vertebral fragility and that therapies that improve both vertebral cortical and trabecular bone properties may provide a greater reduction in fracture risk. © 2010 American Society for Bone and Mineral Research     

Human parathyroid hormone (1-34) increases mass and structure of the cortical shell,with resultant increase in lumbar bone strength,in ovariectomized rats

Estrogen deficiency causes reduction of bone mass and abnormal bone microarchitecture, consequently reducing bone strength. Human parathyroid hormone (hPTH) (1-34) increases bone mass and strength. To clarify the factors that determine the recovery of bone strength in the lumbar vertebrae of ovariectomized rats by intermittent hPTH administration, we analyzed the relationship between skeletal measurements and bone strength. Human PTH (1-34) administration resulted in recovery of cortical bone mineral content (BMC) and cortical bone area to sham the levels, but in resulted in a less pronounced recovery of trabecular BMC and no increase in the total cross-sectional area of the vertebral body. Of the three-dimensional (3D) trabecular bone parameters, hPTH (1-34) increased trabecular thickness (Tb.Th). The cortical shell area of L4, determined by histomorphometry, was also increased. In hPTH-treated rats, the only determinant of the compressive load of L5 was the cortical shell BMC, in the early recovery period (days 42–84). Our data suggest that increased cortical bone mass contributes more than trabecular bone mass and structure to the recovery of bone strength in response to hPTH therapy in the rat lumbar vertebral body after ovariectomy.     

Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure.

Histomorphometry and microCT of 51 paired iliac crest biopsy specimens from women treated with teriparatide revealed significant increases in cancellous bone volume, cancellous bone connectivity density, cancellous bone plate-like structure, and cortical thickness, and a reduction in marrow star volume. INTRODUCTION: We studied the ability of teriparatide (rDNA origin) injection [rhPTH(1-34), TPTD] to improve both cancellous and cortical bone in a subset of women enrolled in the Fracture Prevention Trial of postmenopausal women with osteoporosis after a mean treatment time of 19 months. This is the first report of a biopsy study after treatment with teriparatide having a sufficient number of paired biopsy samples to provide quantitative structural data. METHODS: Fifty-one paired iliac crest bone biopsy specimens (placebo [n = 19], 20 microg teriparatide [n = 18], and 40 microg teriparatide [n = 14]) were analyzed using both two-dimensional (2D) histomorphometry and three-dimensional (3D) microcomputed tomography (microCT). Data for both teriparatide treatment groups were pooled for analysis. RESULTS AND CONCLUSIONS: By 2D histomorphometric analyses, teriparatide significantly increased cancellous bone volume (median percent change: teriparatide, 14%; placebo, -24%; p = 0.001) and reduced marrow star volume (teriparatide, -16%; placebo, 112%; p = 0.004). Teriparatide administration was not associated with osteomalacia or woven bone, and there were no significant changes in mineral appositional rate or wall thickness. By 3D cancellous and cortical bone structural analyses, teriparatide significantly decreased the cancellous structure model index (teriparatide, -12%; placebo, 7%; p = 0.025), increased cancellous connectivity density (teriparatide, 19%; placebo, - 14%; p = 0.034), and increased cortical thickness (teriparatide, 22%; placebo, 3%; p = 0.012). These data show that teriparatide treatment of postmenopausal women with osteoporosis significantly increased cancellous bone volume and connectivity, improved trabecular morphology with a shift toward a more plate-like structure, and increased cortical bone thickness. These changes in cancellous and cortical bone morphology should improve biomechanical competence and are consistent with the substantially reduced incidences of vertebral and nonvertebral fractures during administration of teriparatide.     

Intervertebral disc disorganization is related to trabecular bone architecture in the lumbar spine.

Cancellous bone morphometry was investigated in the sagittal plane of lumbar vertebrae using histoquantitation. The aim of this study was to identify variations in cancellous bone architecture at increasing states of intervertebral disc (IVD) disorganization after age adjustment and to investigate regional variations within the whole vertebral body. Measurements were taken of the ratio of bone volume (BV) to total volume (TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and trabecular number (Tb.N). Lumbar spines (T12-L5) of 19 men and 8 women were removed at autopsy from an adult sample with no clinical history of bone-related disease or histologically identifiable bone disease. It was found that degeneration of the IVD becomes more common with increasing age. After age-adjustment, significant increases in the proportion of BV/TV were observed in the presence of advancing IVD disorganization. Significant architectural changes were observed in the anterior regions of the vertebral body with increases in Tb.Th and Tb.N and decreases in Tb.Sp. Minimal alterations were found at posterior regions. Bone loss was observed in central regions (most distant from the cortex) as IVD disorganization increased through reduction in both Tb.N and Tb.Th. The BV/TV increase in anterior areas of the centrum may be a response to a redistribution of load to the vertebral body periphery as a result of IVD disorganization. It appears that trabecular morphology is related to the condition of the associated IVD, rather than being the sole consequence of a loss of BV/TV with age. This relationship could influence the occurrence of vertebral body crush fracture.     

Proportion of human vertebral body bone that is cancellous

The concept that vertebral fractures are caused by excessive loss of cancellous bone has been challenged by a recent study (J Bone Min Res 2:221, 1987) suggesting that vertebral bodies are composed mainly of cortical bone rather than cancellous bone. To resolve disagreement we used two independent methods to quantify the proportions of cortical and cancellous bone in 400 microns thick sections of the bodies of the second lumbar vertebrae from six men (aged 21-58 years) and seven women (aged 25-58 years). Based on the ash weight of the manually dissected components, 80% of the total bone in men and 72% in women was cancellous bone. Based on computer-assisted scanning of sections with a microdensitometer, 81% of the total bone in men and 71% in women was cancellous bone. We conclude that the traditional concept is correct: the vertebral body is composed mainly of cancellous bone.     

Bone three-dimensional microstructural features of the common osteoporotic fracture sites

Osteoporosis is a common metabolic skeletal disorder characterized by decreased bone mass and deteriorated bone structure, leading to increased susceptibility to fractures. With aging population, osteoporotic fractures are of global health and socioeconomic importance. The three-dimensional microstructural information of the common osteoporosis-related fracture sites, including vertebra, femoral neck and distal radius, is a key for fully understanding osteoporosis pathogenesis and predicting the fracture risk. Low vertebral bone mineral density (BMD) is correlated with increased fracture of the spine. Vertebral BMD decreases from cervical to lumbar spine, with the lowest BMD at the third lumbar vertebra. Trabecular bone mass of the vertebrae is much lower than that of the peripheral bone. Cancellous bone of the vertebral body has a complex heterogeneous three-dimensional microstructure, with lower bone volume in the central and anterior superior regions. Trabecular bone quality is a key element to maintain the vertebral strength. The increased fragility of osteoporotic femoral neck is attributed to low cancellous bone volume and high compact porosity. Compared with age-matched controls, increased cortical porosity is observed at the femoral neck in osteoporotic fracture patients. Distal radius demonstrates spatial inhomogeneous characteristic in cortical microstructure. The medial region of the distal radius displays the highest cortical porosity compared with the lateral, anterior and posterior regions. Bone strength of the distal radius is mainly determined by cortical porosity, which deteriorates with advancing age.     

An evaluation of bone mineral mass and trabecular distribution on cross sections of thoracic and lumbar vertebral bodies

Quantitative computed tomography (QCT) has come into wide use. However, it is difficult to evaluate the bone mineral density of the thoracic vertebral body by QCT, because of the influence of the lungs, the difficulty in positioning etc. In this study, the CT-value and trabecular distribution of the bone area in the undecalcified section of the 8th thoracic, the 12th thoracic and the 3rd lumbar vertebral body were examined. As a result, no difference in bone mineral density and trabecular distribution of these vertebral bodies was recognized. In all vertebral bodies, moreover, the bone area was greater in the posterior part of the vertebral body than in the anterior part. Examining the correlation between age and trabecular distribution, trabeculae in the 12th thoracic vertebral body and the 3rd lumbar vertebral body similarly decreased with age.     

Anabolic action of parathyroid hormone on cortical and cancellous bone differs between axial and appendicular skeletal sites in mice

The mouse is being increasingly used to study the anabolic action of parathyroid hormone (PTH) on the skeleton. The efficacy of intermittent PTH treatment on bone varies widely among tested strains of mice with differences in peak bone mass and structure. We have therefore examined the responses of skeletal sites with high or low cancellous bone mass to PTH treatment in a single strain with genetically low bone mass. Mature C57BL/6 mice were ovariectomized (ovx) or sham operated and, after 4 weeks, treated with PTH(1-34) (40 microg/kg/day, 5 days/week sc) or vehicle for 3 or 7 weeks. Two doses of fluorescent labels were given to the animals 9 and 3 days before euthanasia. Histomorphometry was performed on sections of the proximal tibia, tibial diaphysis, and vertebral body. The results indicate that 4 to 11 weeks of ovx induced a approximately 44% loss of cancellous bone in the proximal tibia and a approximately 25% loss of cancellous bone in the vertebra with impaired trabecular architecture and high bone turnover. In the intact animals, PTH increased cancellous bone volume to a greater extent in the vertebral body than in the proximal tibia, a site with lower cancellous bone volume at the outset. In the ovx mice, PTH increased cancellous bone volume to a greater extent in the vertebral body, a site displaying moderate cancellous bone loss, than in the proximal tibia, a site with severe cancellous bone loss. Conversely, the treatment added a little cortical bone to the tibia, a highly loaded site, but did not significantly increase cortical width of the vertebral body, a less loaded site. We conclude that, for intermittent PTH treatment to be maximally effective, there must be an adequate number of trabeculae present at the beginning of treatment, regardless of estrogen status. Our results also support an interaction between PTH anabolic action and mechanical loading.