Bone mineral and stiffness loss at the distal femur and proximal tibia in acute spinal cord injury

Summary

Computed tomography and finite element modeling were used to assess bone mineral and stiffness loss at the knee following acute spinal cord injury (SCI). Marked bone mineral loss was observed from a combination of trabecular and endocortical resorption. Reductions in stiffness were 2-fold greater than reductions in integral bone mineral.

Introduction

SCI is associated with a rapid loss of bone mineral and an increased rate of fragility fracture. The large majority of these fractures occur around regions of the knee. Our purpose was to quantify changes to bone mineral, geometry, strength indices, and stiffness at the distal femur and proximal tibia in acute SCI.

Methods

Quantitative computed tomography (QCT) and patient-specific finite element analysis were performed on 13 subjects with acute SCI at serial time points separated by a mean of 3.5 months (range 2.6–4.8 months). Changes in bone mineral content (BMC) and volumetric bone mineral density (vBMD) were quantified for integral, trabecular, and cortical bone at epiphyseal, metaphyseal, and diaphyseal regions of the distal femur and proximal tibia. Changes in bone volumes, cross-sectional areas, strength indices and stiffness were also determined.

Results

Bone mineral loss was similar in magnitude at the distal femur and proximal tibia. Reductions were most pronounced at epiphyseal regions, ranging from 3.0 % to 3.6 % per month for integral BMC (p?<?0.001) and from 2.8 % to 3.4 % per month (p?<?0.001) for integral vBMC. Trabecular BMC decreased by 3.1–4.4 %/month (p?<?0.001) and trabecular vBMD by 2.7–4.7 %/month (p?<?0.001). A 3.8–5.4 %/month reduction was observed for cortical BMC (p?<?0.001); the reduction in cortical vBMD was noticeably lower (0.6–0.8 %/month; p?≤?0.01). The cortical bone loss occurred primarily through endosteal resorption, and reductions in strength indices and stiffness were some 2-fold greater than reductions in integral bone mineral.

Conclusions

These findings highlight the need for therapeutic interventions targeting both trabecular and endocortical bone mineral preservation in acute SCI.     

An Exploratory Study of the Texture Research Investigational Platform (TRIP) to Evaluate Bone Texture Score of Distal Femur DXA Scans – A TBS-Based Approach

Poor bone status is associated with increased complications following orthopedic surgery. Therefore, assessing site-specific skeletal status prior to or after orthopedic surgery to optimize outcomes is appealing. The trabecular bone score (TBS) approach, a surrogate for microarchitecture, was adapted to the Texture Research Investigational Platform (TRIP), which allows assessment of many skeletal sites imaged by various modalities. TRIP generates a bone texture score (TBS ORTHO), which could potentially guide surgical decision-making and offer insight into postsurgical fracture risk. As distal femur bone loss occurs following total knee arthroplasty (TKA), we hypothesized that TBS ORTHO after TKA would identify poorer texture in the operated femur compared to the nonoperated. We evaluated 30 subjects (15 M/15 F) with unilateral TKA 2–5 yr previously, mean age 67.9 yr and body mass index 30 kg/m². Using a Lunar iDXA, lumbar spine and entire femur scans were obtained, the latter using the atypical femur fracture feature. Distal femur bone mineral density (BMD) and TBS ORTHO were obtained using manual regions of interest (ROI) at 15% and 25% of leg length from the intercondylar notch. TBS ORTHO was determined using distal femur DICOM images and TRIP v1.0 (Medimaps, France). Differences in operated vs nonoperated femur were evaluated by paired t test. As previously reported, operated leg BMD was approx 10% lower at 15% and 25% ROIs. Similarly, TBS ORTHO values in the operated leg were approx 5% lower (p < 0.05) at these same ROIs. Distal femur TBS ORTHO and BMD were largely unrelated. TBS ORTHO reproducibility at these ROIs was approx 3.5%. In conclusion, this pilot study documents the feasibility of reproducibly obtaining distal femur TBS ORTHO values. Lower values were observed in the surgical leg, consistent with the bone loss that follows TKA. Further work is indicated to refine TRIP use and evaluate whether such data provides guidance for surgical decision-making and improves periprosthetic fracture prediction.     

Assessment of Bone Mineral Density at the Distal Femur and the Proximal Tibia by Dual-Energy X-ray Absorptiometry in Individuals With Spinal Cord Injury: Precision of Protocol and Relation to Injury Duration

Spinal cord injury (SCI) is characterized by marked bone loss at the knee, and there is a need for established dual-energy X-ray absorptiometry (DXA) protocols to examine bone mineral density (BMD) at this location to track therapeutic progress and to monitor fracture risk. The purpose of this study was to quantify the precision and reliability of a DXA protocol for BMD assessment at the distal femur and the proximal tibia in individuals with SCI. The protocol was subsequently used to investigate the relationship between BMD and duration of SCI. Nine individuals with complete SCI and 9 able-bodied controls underwent 3 repeat DXA scans in accordance with the short-term precision methodology recommended by the International Society of Clinical Densitometry. The DXA protocol demonstrated a high degree of precision with the root-mean-square standard deviation ranging from 0.004 to 0.052?g/cm² and the root-mean-square coefficient of variation ranging from 0.6% to 4.4%, depending on the bone, the region of interest, and the rater. All measurements of intra- and inter-rater reliability were excellent with an intraclass correlation of ≥0.950. The relationship between the BMD and the duration of SCI was well described by a logarithmic trend (r²?=?0.68–0.92). Depending on the region of interest, the logarithmic trends would predict that, after 3?yr of SCI, BMD at the knee would be 43%–19% lower than that in the able-bodied reference group. We believe the DXA protocol has the level of precision and reliability required for short-term assessments of BMD at the distal femur and the proximal tibia in people with SCI. However, further work is required to determine the degree to which this protocol may be used to assess longitudinal changes in BMD after SCI to examine clinical interventions and to monitor fracture risk.     

Lower trabecular volumetric BMD at metaphyseal regions of weight‐bearing bones is associated with prior fracture in young girls

Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump‐In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual‐energy X‐ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1–1.9) and 1.3 (1.0–1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. © 2011 American Society for Bone and Mineral Research.     

Speed of sound in bone at the tibia: is it related to lower limb bone mineral density in spinal-cord-injured individuals?

STUDY DESIGN: A cross-sectional study evaluating BMD at the hip and tibia, and SOS at the radius and mid-tibia in individuals with spinal cord injury (SCI) and a subgroup of non-SCI individuals. OBJECTIVES: To investigate the speed of sound (SOS) in bone in relation to bone mineral density (BMD). SETTING: Kinesiology Department, McMaster University, Ontario, Canada. METHODS: In 14 individuals with SCI and 10 non-SCI individuals, proximal femur and tibia BMD were measured using dual energy X-ray absorptiometry, and radius and tibia SOS were measured with an ultrasonometer. T-scores were calculated using healthy reference databases. Inter-relationships between measurement techniques were determined using Pearson's correlation coefficients. P-values less than 0.05 were considered statistically significant. RESULTS:: The average ages of the SCI and non-SCI groups were 33+/-9 and 27+/-6 years, respectively. Lesion level ranged from C4 to T12 and average time postinjury was 12 years, with a range of 1.6-25 years. Using the WHO criteria for osteoporosis, nine of 14 SCI subjects were osteoporotic at the hip, with the remainder in the osteopenic range. Tibia SOS T-scores were in the osteoporotic range for one subject with SCI, and two were in the osteopenic range. Among non-SCI individuals, one male had a tibia SOS T-score of -1.4, all others were within the normal range. Hip BMD and tibia SOS were significantly correlated (r=0.46, P<0.01). Hip BMD and tibia BMD were more strongly correlated (r=0.80, P<0.0005). Tibia BMD was not significantly correlated with SOS at the tibia (r=0.35, P=0.09). Radius SOS T-scores were positive and not significantly correlated with any lower limb variable. CONCLUSION: Lower-limb bone mass is reduced in spinal cord-injured individuals, but SOS at the mid-tibia is not. It remains to be determined whether ultrasound measurements can predict fracture in the SCI population.     

Trabecular bone microarchitecture is deteriorated in men with spinal cord injury.

Using magnetic resonance imaging, men with spinal cord injury (n = 10) were found to have fewer trabeculae that were spaced further apart in the knee than able-bodied controls of similar age, height, and weight (n = 8). The deteriorated trabecular bone microarchitecture may contribute to the increased fracture incidence after injury. INTRODUCTION: Spinal cord injury results in a dramatic decline in areal bone mineral density (aBMD) and a marked increase in lower extremity fracture; however, its effect on trabecular bone microarchitecture is unknown. The purpose of this study was to determine if trabecular bone microarchitecture is deteriorated in the knee of men with long-term, complete spinal cord injury. MATERIALS AND METHODS: Apparent bone volume to total volume (appBV/TV), trabecular number, (appTb.N), trabecular thickness (appTb.Th), and trabecular separation (appTb.Sp), measures of trabecular bone microarchitecture, were assessed in the distal femur and proximal tibia of men with long-term (>2 years) complete spinal cord injury (SCI; n = 10) and able-bodied controls (CON; n = 8) using high-resolution magnetic resonance imaging. Proximal tibia and arm aBMD were determined using DXA. Independent t-tests were used to assess group differences in anthropometrics and bone parameters. Pearson correlation analysis was used to assess the relationships among trabecular bone microarchitecture, aBMD, and time since injury. RESULTS: There were no group differences in age, height, or weight; however, the distal femur and proximal tibia of SCI had 27% and 20% lower appBV/TV, 21% and 20% lower appTb.N, and 44% and 33% higher appTb.Sp, respectively (p < 0.05). The distal femur of SCI also had 8% lower appTb.Th (p < 0.05). Whereas arm aBMD was not different in the two groups, proximal tibia aBMD was 43% lower in SCI. In SCI and CON combined, aBMD was correlated with appBV/TV (r = 0.62), appTb.N (r = 0.78), and appTb.Sp (r = -0.82) in the proximal tibia (p < 0.05). Time since injury was more strongly correlated with appTb.N (r = -0.54) and appTb.Sp (r = 0.56) than aBMD (r = -0.36) in the distal tibia, although none of the relationships were statistically significant (p > 0.05). CONCLUSION: Men with complete spinal cord injury have markedly deteriorated trabecular bone microarchitecture in the knee, which may contribute to their increased fracture incidence.     

Associations of Circulating Levels of Sphingosine 1-Phosphate with the Trabecular Bone Score and Bone Mineral Density in Postmenopausal Women

Despite the potential roles of sphingosine 1-phosphate (S1P) as a biomarker of osteoporotic fracture (OF), independent of bone mineral density (BMD) and clinical risk factors (CRFs), its association with bone microarchitecture, a key determinant of bone quality, have not been studied yet. We here investigated the association of S1P with the trabecular bone score (TBS), an index of the bone microarchitecture. The plasma S1P concentrations, TBS, and BMD were measured in the 339 postmenopausal women. The S1P level was inversely correlated with the TBS (γ=–0.096, p=0.049) and BMD at the femur neck (FN-BMD: γ=–0.122, p=0.025) and tended to be inversely correlated the BMD at the total hip (TH-BMD: γ=–0.096, p=0.079), but not at the lumbar spine (LS-BMD). After adjusting for fracture risk assessment tool probabilities of major OF from CRFs, the S1P level was inversely associated with the TBS (β=–0.096, p=0.049) and FN-BMD (β=–0.118, p=0.025) and tended to be inversely associated with the TH-BMD (β=–0.092, p=0.083). Compared with subjects in the lowest S1P tertile, those in the highest S1P tertile had a significantly lower TBS (p=0.032) and BMD at femur (p=0.004–0.036). These findings indicated that a high S1P level in postmenopausal women was inversely associated with the both bone mass and microarchitecture, reflecting the compromised bone strength.     

Bone morphology of the femur and tibia captured by statistical shape modelling predicts rapid bone loss in acute spinal cord injury patients

After spinal cord injury (SCI), bone loss in the paralysed limbs progresses at variable rates. Decreases in bone mineral density (BMD) in the first year range from 1% (slow) to 40% (rapid). In chronic SCI, fragility fractures commonly occur around the knee, with significant associated morbidity. Osteoporosis treatments await full evaluation in SCI, but should be initiated early and targeted towards patients exhibiting rapid bone loss. The potential to predict rapid bone loss from a single bone scan within weeks of a SCI was investigated using statistical shape modelling (SSM) of bone morphology, hypothesis: baseline bone shape predicts bone loss at 12-months post-injury at fracture-prone sites.In this retrospective cohort study 25 SCI patients (median age, 33 years) were scanned at the distal femur and proximal tibia using peripheral Quantitative Computed Tomography at < 5 weeks (baseline), 4, 8 and 12 months post-injury. An SSM was made for each bone. Links between the baseline shape-modes and 12-month total and trabecular BMD loss were analysed using multiple linear regression.One mode from each SSM significantly predicted bone loss (age-adjusted P < 0.05 R² = 0.37–0.61) at baseline. An elongated intercondylar femoral notch (femur mode 4, + 1 SD from the mean) was associated with 8.2% additional loss of femoral trabecular BMD at 12-months. A more concave posterior tibial fossa (tibia mode 3, + 1 SD) was associated with 9.4% additional 12-month tibial trabecular BMD loss.Baseline bone shape determined from a single bone scan is a valid imaging biomarker for the prediction of 12-month bone loss in SCI patients.     

Long-term HIV infection and antiretroviral therapy are associated with bone microstructure alterations in premenopausal women

Summary

We evaluated the influence of long-term HIV infection and its treatment on distal tibia and radius microstructure. Premenopausal eumenorrheic HIV-positive women displayed trabecular and cortical microstructure alterations, which could contribute to increased bone fragility in those patients.

Introduction

Bone fragility is an emerging issue in HIV-infected patients. Dual-energy X-ray absorptiometry (DXA) quantified areal bone mineral density (BMD) predicts fracture risk, but a significant proportion of fracture risk results from microstructural alterations.

Methods

We studied the influence of long-term HIV infection on bone microstructure as evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 22 HIV-positive (+ve) premenopausal eumenorrheic women and 44 age- and body mass index (BMI)-matched HIV-negative (?ve) controls. All subjects completed questionnaires regarding calcium/protein intakes and physical activity, and underwent DXA and HR-pQCT examinations for BMD and peripheral skeleton microstructure, respectively. A risk factor analysis of tibia trabecular density using linear mixed models was conducted.

Results

In HIV+ve women on successful antiretroviral therapy (undetectable HIV-RNA, median CD4 cell count, 626), infection duration was 16.5?±?3.5 (mean ± SD)?years; median BMI was 22 (IQR, 21–26)?kg/m². More HIV+ve women were smokers (82 versus 50 %, p?=?0.013). Compared to controls, HIV+ve women had lower lumbar spine (spine T-score ?0.70 vs ?0.03, p?=?0.014), but similar proximal femur BMD. At distal tibia, HIV+ve women had a 14.1 % lower trabecular density and a 13.2 % reduction in trabecular number compared to HIV?ve women (p?=?0.013 and 0.029, respectively). HR-pQCT differences in distal radius were significant for cortical density (?3.0 %; p?=?0.029).

Conclusions

Compared with HIV?ve subjects, premenopausal HIV+ve treated women had trabecular and cortical bone alterations. Adjusted analysis revealed that HIV status was the only determinant of between group tibia trabecular density differences. The latter could contribute to increased bone fragility in HIV+ve patients.     

The predictive value of trabecular bone score (TBS) on whole lumbar vertebrae mechanics: an ex vivo study

Summary

We investigated the association of trabecular bone score (TBS) with microarchitecture and mechanical behavior of human lumbar vertebrae. We found that TBS reflects vertebral trabecular microarchitecture and is an independent predictor of vertebral mechanics. However, the addition of TBS to areal BMD (aBMD) did not significantly improve prediction of vertebral strength.

Introduction

The trabecular bone score (TBS) is a gray-level measure of texture using a modified experimental variogram which can be extracted from dual-energy X-ray absorptiometry (DXA) images. The current study aimed to confirm whether TBS is associated with trabecular microarchitecture and mechanics of human lumbar vertebrae, and if its combination with BMD improves prediction of fracture risk.

Methods

Lumbar vertebrae (L3) were harvested fresh from 16 donors. The anteroposterior and lateral bone mineral content (BMC) and areal BMD (aBMD) of the vertebral body were measured using DXA; then, the TBS was extracted using TBS iNsight software (Medimaps SA, France). The trabecular bone volume (Tb.BV/tissue volume, TV), trabecular thickness (Tb.Th), degree of anisotropy, and structure model index (SMI) were measured using microcomputed tomography. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies to assess failure load and stiffness.

Results

The TBS was significantly correlated to Tb.BV/TV and SMI (r?=?0.58 and ?0.62; p?=?0.02, 0.01), but not related to BMC and BMD. TBS was significantly correlated with stiffness (r?=?0.64; p?=?0.007), independently of bone mass. Using stepwise multiple regression models, we failed to demonstrate that the combination of BMD and TBS was better at explaining mechanical behavior than either variable alone. However, the combination TBS, Tb.Th, and BMC did perform better than each parameter alone, explaining 79 % of the variability in stiffness.

Conclusions

In our study, TBS was associated with microarchitecture parameters and with vertebral mechanical behavior, but TBS did not improve prediction of vertebral biomechanical properties in addition to aBMD.     

Bone quality assessment in type 2 diabetes mellitus

Summary

The increased risk for fractures in type 2 diabetes mellitus (T2DM) despite higher average bone density is unexplained. This study assessed trabecular bone quality in T2DM using the trabecular bone score (TBS). The salient findings are that TBS is decreased in T2DM and low TBS associates with worse glycemic control.

Introduction

Type 2 diabetes mellitus is a risk factor for osteoporotic fractures despite high average bone mineral density (BMD). The aim of this study was to compare BMD with a noninvasive assessment of trabecular microarchitecture, TBS, in women with T2DM.

Methods

In a cross-sectional study, trabecular microarchitecture was examined in 57 women with T2DM and 43 women without diabetes, ages 30 to 90 years. Lumbar spine BMD was measured by dual-emission x-ray absorptiometry (DXA), and TBS was calculated by examining pixel variations within the DXA images utilizing TBS iNsight software.

Results

Mean TBS was lower in T2DM (1.228?±?0.140 vs. 1.298?±?0.132, p?=?0.013), irrespective of age. Mean BMD was higher in T2DM (1.150?±?0.172 vs. 1.051?±?0.125, p?=?0.001). Within the T2DM group, TBS was higher (1.254?±?0.148) in subjects with good glycemic control (A1c?≤?7.5 %) compared to those (1.166?±?0.094; p?=?0.01) with poor glycemic control (A1c?>?7.5 %).

Conclusion

In T2DM, TBS is lower and associated with poor glycemic control. Abnormal trabecular microarchitecture may help explain the paradox of increased fractures at a higher BMD in T2DM. Further studies are needed to better understand the relationship between glycemic control and trabecular bone quality.     

Femur and Tibia BMD Measurement in Elective Total Knee Arthroplasty Candidates

Distal femur BMD declines ～20% following total knee arthroplasty (TKA) potentially leading to adverse outcomes. BMD knowledge before and following TKA might allow interventions to optimize outcomes. We hypothesized that distal femur and proximal tibial BMD could be reproducibly measured with existing DXA technology. Elective TKA candidates were enrolled and standard clinical DXA plus bilateral PA and lateral knee scans acquired. Manual regions of interest (ROIs) were placed at distal femur and proximal tibia sites based on required TKA machining and periprosthetic fracture location. Intra- and inter-rater BMD reliability was assessed by intra-class correlation (ICC). Custom and standard proximal femur BMD were correlated by linear regression and paired t test evaluated BMD differences between planned surgical and contralateral side. One hundred subjects (68F/32M), mean (SD) age and BMI of 67.2 (7.7) yr and 30.8 (4.8) kg/m² were enrolled. Lowest clinical BMD T-score was < -1.0 in 65% and ≤ -2.5 in 16%; 34 had prior fracture. BMD reproducibility at all custom ROIs was excellent; ICC > 0.96. Mean BMD at custom ROIs ranged from 0.903 to 1.346 g/cm² in the PA projection and 0.891 to 1.429 g/cm² in the lateral. Lower BMD values were observed at the proximal tibia, while the higher measurements were at the femur condyle. Custom knee ROI BMD was highly correlated (p < 0.0001) with total and femur neck with better correlation at ROIs adjacent to the joint (R² = 0.62–0.67, 0.49–0.55 respectively). In those without prior TKA (n = 76), mean BMD was lower (2.8%–6.6%; p < 0.05) in the planned surgical leg at all custom ROIs except the PA tibial regions. Individual variability was present with 82% having a custom ROI with lower BMD (up to 53%) in the planned operative leg. Distal femur and proximal tibial BMD can be measured using custom ROIs with good reproducibility. Suboptimal bone status is common in TKA candidates and distal femur/proximal tibia BMD is often lower on the planned operative side. Routine distal femur/proximal tibial BMD measurement might assist pre-operative interventions, surgical decision-making, subsequent care and outcomes. Studies to evaluate these possibilities are indicated.     

Bone impairment assessed by HR-pQCT in juvenile-onset systemic lupus erythematosus

Summary

High-resolution peripheral quantitative computed tomography (HR-pQCT) analysis of female juvenile-onset systemic lupus erythematosus (JoSLE) patients revealed trabecular/cortical bone damage and reduced bone strength primarily at the distal radius compared to healthy controls. We demonstrated for the first time that JoSLE patients with vertebral fracture (VF) present trabecular impairment at the distal radius.

Introduction

This study investigated the volumetric bone mineral density (vBMD), microarchitecture, and biomechanical features at the distal radius and tibia using HR-pQCT and laboratory bone markers in JoSLE patients compared to controls to determine whether this method discriminates JoSLE patients with or without VF.

Methods

We compared 56 female JoSLE patients to age- and Tanner-matched healthy controls. HR-pQCT was performed at the distal radius and tibia. Serum levels of the amino-terminal pro-peptide of type I collagen, the C-terminal telopeptide of type I collagen, intact parathormone, sclerostin, and 25-hydroxyvitamin D (25OHD) were evaluated. VFs were analyzed using VFA-dual-energy X-ray absorptiometry (DXA) (Genant’s method).

Results

Reduced density and strength parameters and microarchitecture alterations of cortical and trabecular bones were observed in JoSLE patients compared to controls, primarily at the distal radius (p?<?0.05). Patients with VF exhibited a significant decrease in trabecular bone parameters solely at the distal radius (Total.BMD, p?=?0.034; Trabecular.BMD [Tb.BMD], p?=?0.034; bone volume (BV)/trabecular volume (TV), p?=?0.034; apparent modulus, p?=?0.039) and higher scores for disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI), p?=?0.002). Bone metabolism markers were similar in all groups. Logistic regression analysis of parameters that were significant in univariate analysis revealed that Tb.BMD (OR 0.98, 95 % CI 0.95–0.99, p?=?0.039) and SLICC/ACR-DI (OR 7.37, 95 % CI 1.75–30.97, p?=?0.006) were independent risk factors for VF.

Conclusion

In conclusion, this study is the first demonstration of bone microstructure and strength deficits in JoSLE patients, particularly at the distal radius. Our results demonstrated that VF was associated with trabecular radius alteration and emphasized the potential detrimental effect of disease damage on this condition.

     

Trabecular bone is more deteriorated in spinal cord injured versus estrogen-free postmenopausal women

The prevalence of osteoporosis is high among postmenopausal women and individuals sustaining a spinal cord injury (SCI). We assessed the effects of estrogen loss and unloading on the trabecular bone of the knee in women. Pre- and postmenopausal ambulatory women (n=17) were compared to pre- and postmenopausal women with SCI (n=20). High-resolution magnetic resonance imaging was used to compare groups on apparent measures of trabecular bone volume, trabecular number, trabecular spacing, and trabecular thickness in the distal femur and proximal tibia, regions with a high proportion of trabecular bone and the most common fracture site for SCI patients. Trabecular bone was deteriorated in women with SCI compared to ambulatory women. SCI groups had fewer, (–19 and –26% less) and thinner trabeculae (–6%) that were spaced further apart (40% and 62% more space between structures) resulting in less trabecular bone volume (–22% and –33%) compared to the ambulatory groups (tibia and femur, respectively). Postmenopausal women with SCI also had 34% greater trabecular spacing in the tibia compared to the 40-year-old premenopausal women with SCI, showing an interaction between unloading and estrogen loss. Middle-aged postmenopausal, ambulatory women, not taking estrogen or medications that affect bone, did not show the deteriorated trabeculae that were evident in women with SCI, nor did they show differences in distal femur and proximal tibia trabeculae compared to a premenopausal group. We conclude that the effect of unloading on bone architecture is greater than that of estrogen loss in middle-aged women.     

Skeletal Benefits After Long‐Term Retirement in Former Elite Female Gymnasts

Bone strength benefits after long‐term retirement from elite gymnastics in terms of bone geometry and volumetric BMD were studied by comparing retired female gymnasts to moderately active age‐matched women. In a cross‐sectional study, 30 retired female gymnasts were compared with 30 age‐matched moderately active controls. Bone geometric and densitometric parameters were measured by pQCT at the distal epiphyses and shafts of the tibia, femur, radius, and humerus. Muscle cross‐sectional areas were assessed from the shaft scans. Independent t‐tests were conducted on bone and muscle variables to detect differences between the two groups. The gymnasts had retired for a mean of 6.1 ± 0.4 yr and were engaged in ≤2 h of exercise per week since retirement. At the radial and humeral shafts, cortical cross‐sectional area (CSA), total CSA, BMC, and strength strain index (SSIpol) were significantly greater (13–38%, p ≤ 0.01) in the retired gymnasts; likewise, BMC and total CSA were significantly greater at the distal radius (22–25%, p ≤ 0.0001). In the lower limbs, total CSA and BMC at the femur and tibia shaft were greater by 8–11%, and trabecular BMD and BMC were only greater at the tibia (7–8%). Muscle CSA at the forearm and upper arm was greater by 15–17.6% (p ≤ 0.001) but was not different at the upper and lower leg. Past gymnastics training is associated with greater bone mass and bone size in women 6 yr after retirement. Skeletal benefits were site specific, with greater geometric adaptations (greater bone size) in the upper compared with the lower limbs.     

Genetic variations that regulate bone morphology in the male mouse skeleton do not define its susceptibility to mechanical unloading

Genetics can substantially influence bone morphology and may define the skeleton's response to mechanical unloading. Recent data indicated that disuse produces different site-specific responses in the skeleton of genetically distinct adult female C3H/HeJ (C3H) and BALB/cByJ (BALB) mice; while disuse BALB mice had significantly less bone than age-matched controls in the distal and diaphyseal femur, the removal of weight bearing had a much smaller influence in C3H. Using adult male mice from these two inbred strains, the hypothesis was tested that interactions between genetic variations and anatomic location define bone morphology and its susceptibility to unloading. Four-month-old male BALB and C3H mice were either subjected to 21 days of hindlimb unloading or served as controls. Multiple cortical and trabecular regions within the distal and diaphyseal femur were analyzed by micro-computed tomography. C3H controls had significantly greater diaphyseal and metaphyseal cortical bone area (45% and 32%) and greater metaphyseal trabecular bone volume fraction (67%) than BALB controls, but epiphyseal trabecular bone volume fraction was similar between the two strains. Despite these substantial, site-specific differences in bone morphology, disuse induced similar changes in bone morphology in these two strains. Compared to controls, disuse BALB and C3H had significantly less metaphyseal (17% and 19%) and epiphyseal (10% and 13%) trabecular bone, while diaphyseal and metaphyseal cortical bone geometry was unaffected. These data indicate that the genetic variations that caused spatially nonuniform differences in trabecular and cortical bone morphology between the two strains had little influence on the susceptibility of a specific site to unloading. Cross-gender comparisons with previous data from female BALB and C3H mice further suggest strong interactions by which gender, genotype, and anatomical location define the response of the skeleton to the removal of weight bearing.     

Morphology-mechanical property relations in trabecular bone of the osteoarthritic proximal tibia

Alteration of morphologic and mechanical properties of trabecular bone in the osteoarthritic proximal tibia may be a contributing factor in tibial component loosening. To explore this issue, the authors performed tissue property measurements, morphologic analysis, and mechanical testing of subchondral, epiphyseal, and metaphyseal trabecular bone specimens retrieved from six human proximal tibias exhibiting a range of medial unicondylar osteoarthritic degeneration. Apparent density in the proximal tibia was altered according to varus misalignment and medial subluxation associated with medial osteoarthritis of the knee. In subchondral bone, a decrease in tissue mineralization contributed to a significant reduction in axial mechanical properties with degenerative disease (P < .0005). In epiphyseal and metaphyseal bone, trabecular thickness and the number of trabeculae increased linearly with volume fraction, providing a power law relationship between axial elastic modulus and apparent density (R² = .84). Average elastic properties of the tibial epiphysis and metaphysis were not reduced by degenerative disease (P < .05). The results suggest that absolute minimization of tibial resection might not be an optimal strategy for tibial component fixation and that mechanical properties of the tibial resection surface are more homogeneous in planes parallel to the joint surface than in a plane normal to the longitudinal axis of the tibia.     

Older Age and Higher Body Mass Index Are Associated With a More Degraded Trabecular Bone Score Compared to Bone Mineral Density

Trabecular bone score (TBS) may detect subjects with a more degraded microarchitecture but whose bone mineral density (BMD) reflects normal or osteopenia. The purpose of this study was to evaluate whether age and body sizes were associated with the discordance between BMD and TBS. We analyzed BMD and TBS in 1505 Korean women over 40?yr of age who had no history of osteoporotic fractures or conditions that affect bone metabolism. We considered 3 groups to have TBS values that reflected a more degraded TBS than their BMD values: (1) normal BMD but partially degraded TBS, (2) normal BMD but degraded TBS, and (3) osteopenia but degraded TBS. We compared subjects in these 3 groups with other subjects in terms of age and body sizes, and used multivariable logistic regression to analyze the odds ratios (ORs) for the occurrence of a more degraded TBS than their BMD level using age and body mass index (BMI). One hundred sixty subjects (10.6%) were found to have a more degraded TBS than their BMD level; these subjects were older, heavier, and had higher BMIs than the other subjects. Age (OR: 1.038, 95% confidence interval: 1.020–1.057, p <?0.001) and BMI (OR: 1.223, 95% confidence interval: 1.166–1.283, p <?0.001) were statistically significant in the multivariable analysis for the occurrence of this feature. Women with a more degraded TBS than their BMD level are older and have higher BMIs than the other subjects. It may be helpful to consider the possibility of trabecular bone degradation when clinically evaluating fracture risk in patients who are older or who have high BMIs with normal BMD or osteopenia.     

Bone steady-state is established at reduced bone strength after spinal cord injury: a longitudinal study using peripheral quantitative computed tomography (pQCT)

Spinal cord injury (SCI) is associated with a marked and rapid sublesional bone loss. So far, reports about the time course of adaptive changes in bone mass and structure in people with chronic and complete SCI are conflicting. Both, a continuous decline of bone parameters throughout the chronic phase of immobilisation as well as stabilisation of bone status on a low level have been documented. In our recently published cross-sectional study we suggested that subjects with a complete SCI reach a new bone steady-state in the paralysed limbs after extensive bone loss was complete. In addition, we described a time loss curve for each measured bone mineral density and geometry parameter and calculated its individual time to reach steady-state (tsteady-state). The aim of the present study was to test the findings of our cross-sectional study in a longitudinal design. Thirty-nine male subjects of the original cross-sectional study with complete SCI and paralysis duration between 0.9 and 34 years were included. Two follow-up pQCT measurements at 15 and 30 months after baseline measurement were performed at the distal epiphyses and mid shafts of the femur, tibia and radius. From the epiphyseal scans, bone mass, trabecular and total BMD were calculated. From the shaft scans, bone mass and cortical BMD, total and cortical cross-sectional areas and cortical thickness were determined. Repeated measures ANOVAs were performed with bone data at baseline, after 15 months and 30 months. Analyses were performed including only subjects with a lesion duration > or =t(steady-state) for each particular bone parameter. Bone parameters of tibial and femoral epi- and diaphyses were found to show no statistically significant differences between the three time points. Relative changes in bone parameters were small and ranged from -1.72% to +0.51% in the femur and from -1.67% to +0.42% in the tibia within 30 months of monitoring. Our data confirm the temporal limitation of the bone loss after complete SCI with stabilisation of BMD and geometric properties on a lower level-a finding of clinical importance considering the treatment strategies of bone loss after SCI with respect to lesion duration.