Paul F. Hoffmann

Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of QCT scans in women with osteoporosis.

FE modeling was used to estimate the biomechanical effects of teriparatide and alendronate on lumbar vertebrae. Both treatments enhanced predicted vertebral strength by increasing average density. This effect was more pronounced for teriparatide, which further increased predicted vertebral strength by altering the distribution of density within the vertebra, preferentially increasing the strength of the trabecular compartment.

Femoral Bone Strength and Its Relation to Cortical and Trabecular Changes After Treatment With PTH, Alendronate, and Their Combination as Assessed by Finite Element Analysis of Quantitative CT Scans

The “PTH and Alendronate” or “PaTH” study compared the effects of PTH(1‐84) and/or alendronate (ALN) in 238 postmenopausal, osteoporotic women. We performed finite element analysis on the QCT scans of 162 of these subjects to provide insight into femoral strength changes associated with these treatments and the relative roles of changes in the cortical and trabecular compartments on such strength changes. Patients were assigned to either PTH, ALN, or their combination (CMB) in year 1 and were switched to either ALN or placebo (PLB) treatment in year 2: PTH‐PLB, PTH‐ALN, CMB‐ALN, and ALN‐ALN (year 1‐year 2) treatments. Femoral strength was simulated for a sideways fall using nonlinear finite element analysis of the quantitative CT exams. At year 1, the strength change from baseline was statistically significant for PTH (mean, 2.08%) and ALN (3.60%), and at year 2, significant changes were seen for the PTH‐ALN (7.74%), CMB‐ALN (4.18%), and ALN‐ALN (4.83%) treatment groups but not for PTH‐PLB (1.17%). Strength increases were primarily caused by changes in the trabecular density regardless of treatment group, but changes in cortical density and mass also played a significant role, the degree of which depended on treatment. For PTH treatment at year 1 and for ALN‐ALN treatment at year 2, there were significant negative and positive strength effects, respectively, associated with a change in external bone geometry. Average changes in strength per treatment group were somewhat consistent with average changes in total hip areal BMD as measured by DXA, except for the PTH group at year 1. The relation between change in femoral strength and change in areal BMD was weak (r2 = 0.14, pooled, year 2). We conclude that femoral strength changes with these various treatments were dominated by trabecular changes, and although changes in the cortical bone and overall bone geometry did contribute to femoral strength changes, the extent of these latter effects depended on the type of treatment.

Structural Determinants of Vertebral Fracture Risk

Vertebral fractures are more strongly associated with specific bone density, structure, and strength parameters than with areal BMD, but all of these variables are correlated.

Age-dependence of femoral strength in white women and men.

Although age‐related variations in areal bone mineral density (aBMD) and the prevalence of osteoporosis have been well characterized, there is a paucity of data on femoral strength in the population. Addressing this issue, we used finite‐element analysis of quantitative computed tomographic scans to assess femoral strength in an age‐stratified cohort of 362 women and 317 men, aged 21 to 89 years, randomly sampled from the population of Rochester, MN, and compared femoral strength with femoral neck aBMD. Percent reductions over adulthood were much greater for femoral strength (55% in women, 39% in men) than for femoral neck aBMD (26% in women, 21% in men), an effect that was accentuated in women. Notable declines in strength started in the mid‐40s for women and one decade later for men. At advanced age, most of the strength deficit for women compared with men was a result of this decade‐earlier onset of strength loss for women, this factor being more important than sex‐related differences in peak bone strength and annual rates of bone loss. For both sexes, the prevalence of “low femoral strength” (<3000 N) was much higher than the prevalence of osteoporosis (femoral neck aBMD T‐score of −2.5 or less). We conclude that age‐related declines in femoral strength are much greater than suggested by age‐related declines in femoral neck aBMD. Further, far more of the elderly may be at high risk of hip fracture because of low femoral strength than previously assumed based on the traditional classification of osteoporosis.

Assessment of Incident Spine and Hip Fractures in Women and Men using Finite Element Analysis of CT Scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture.

Vertebral strength changes in rheumatoid arthritis patients treated with alendronate, as assessed by finite element analysis of clinical computed tomography scans: A prospective randomized clinical trial†

OBJECTIVE Finite element analysis of clinical computed tomography (CT) scans provides a noninvasive means of assessing vertebral strength that is superior to dual x-ray absorptiometry (DXA)-measured areal bone mineral density. The present study was undertaken to compare strength changes, measured using this newer method, in rheumatoid arthritis (RA) patients who were treated with alendronate (ALN) versus those who were not. METHODS Thirty female RA patients without radiologic signs of L3 compression fractures or a history of osteoporosis medication were enrolled in a prospective randomized clinical trial. Patients were randomly assigned to the ALN group (5 mg orally, once daily) or the control group not receiving antiresorptive treatment. All patients were evaluated by DXA and quantitative CT at baseline and reevaluated after a mean of 12.2 months. Nonlinear finite element analysis was performed on the CT scans (n = 29 available for analysis) to compute an estimate of vertebral compressive strength and to assess strength changes associated with changes in the trabecular compartment and the outer 2 mm of bone (peripheral compartment). RESULTS On average, vertebral strength was significantly decreased from baseline in the control group (n = 15) (median change -10.6%; P = 0.008) but was maintained in the ALN group (n = 14) (median change +0.4%; P = 0.55), with a significant difference between the 2 groups (P < 0.01). Strength decreased more rapidly within the trabecular bone, and ALN treatment was much more effective in the peripheral than the trabecular compartment. CONCLUSION Our results indicate that patients with RA can lose a substantial amount of vertebral strength over a relatively short period of time, and this loss can be prevented by ALN, primarily via its positive effect on the outer 2 mm of vertebral bone.

Phantomless calibration of CT scans for measurement of BMD and bone strength—Inter-operator reanalysis precision

Patient-specific phantomless calibration of computed tomography (CT) scans has the potential to simplify and expand the use of pre-existing clinical CT for quantitative bone densitometry and bone strength analysis for diagnostic and monitoring purposes. In this study, we quantified the inter-operator reanalysis precision errors for a novel implementation of patient-specific phantomless calibration, using air and either aortic blood or hip adipose tissue as internal calibrating reference materials, and sought to confirm the equivalence between phantomless and (traditional) phantom-based measurements. CT scans of the spine and hip for 25 women and 15 men (mean±SD age of 67±9years, range 41-86years), one scan per anatomic site per patient, were analyzed independently by two analysts using the VirtuOst software (O.N. Diagnostics, Berkeley, CA). The scans were acquired at 120kVp, with a slice thickness/increment of 3mm or less, on nine different CT scanner models across 24 different scanners. The main parameters assessed were areal bone mineral density (BMD) at the hip (total hip and femoral neck), trabecular volumetric BMD at the spine, and vertebral and femoral strength by finite element analysis; other volumetric BMD measures were also assessed. We found that the reanalysis precision errors for all phantomless measurements were ≤0.5%, which was as good as for phantom calibration. Regression analysis indicated equivalence of the phantom- versus phantomless-calibrated measurements (slope not different than unity, R2≥0.98). Of the main parameters assessed, non-significant paired mean differences (n=40) between the two measurements ranged from 0.6% for hip areal BMD to 1.1% for mid-vertebral trabecular BMD. These results indicate that phantom-equivalent measurements of both BMD and finite element-derived bone strength can be reliably obtained from CT scans using patient-specific phantomless calibration.

Prevalence of Poor Bone Quality in Women Undergoing Spinal Fusion Using Biomechanical-ct Analysis

Study Design. Retrospective, cross-sectional analysis of vertebral bone quality in spine-fusion patients at a single medical center. Objective. To characterize the prevalence of osteoporosis and fragile bone strength in a spine-fusion population of women with an age range of 50 years to 70 years. Fragile bone strength is defined as the level of vertebral strength below which a patient is at as high a risk of future vertebral fracture as a patient having bone density-defined osteoporosis. Summary of Background Data. Poor bone quality—defined here as the presence of either osteoporosis or fragile bone strength—is a risk factor for spine-fusion patients that often goes undetected but can now be assessed preoperatively by additional postprocessing of computed tomography (CT) scans originally ordered for perioperative clinical assessment. Methods. Utilizing such perioperative CT scans for a cohort of 98 women (age range: 51–70 yr) about to undergo spine fusion, we retrospectively used a phantomless calibration technique and biomechanical-CT postprocessing analysis to measure vertebral trabecular bone mineral density (BMD) (in mg/cm3) and by nonlinear finite element analysis, vertebral compressive strength (in Newtons, N) in the L1 or L2 vertebra. Preestablished validated threshold values were used to define the presence of osteoporosis (trabecular BMD of 80 mg/cm3 or lower) and fragile bone strength (vertebral strength of 4500 N or lower). Results. Fourteen percent of the women tested positive for osteoporosis, 27% tested positive for fragile bone strength, and 29% were classified as having poor bone quality (either osteoporosis or fragile bone strength). Over this narrow age range, neither BMD nor vertebral strength were significantly correlated with age, weight, height, or body mass index (P values 0.14–0.97 for BMD; 0.13–0.51 for strength). Conclusion. Poor bone quality appears to be common in women between ages 50 years and 70 years undergoing spinal fusion surgery. Level of Evidence: 3