Measuring Apparent Trabecular Structure With pQCT: A Comparison With HR-pQCT

We evaluated how comparable peripheral quantitative computed tomography (pQCT) measurements of cortical thickness, density, and apparent trabecular structure at the ultradistal tibia were with those measured with high-resolution pQCT (HR-pQCT). We also examined whether the accuracy of the pQCT-based trabecular and cortical measurements improved with reductions in slice thickness from the standard 2.2 mm to 1.1 and 0.6 mm. We immersed 15 dry tibia specimens in saline in a sealed cylinder and scanned 22.5 mm from the distal tibia plateau using pQCT and HR-pQCT. pQCT underestimated cortical thickness by Stratec (CTh_Stratec) and trabecular spacing (Tb.Sp) by 21.4% and 72.9%, whereas bone volume to total volume (BV/TV) and cortical density (CDen) were overestimated by 265.8% and 13.1%, respectively. Measurements of trabecular volumetric bone mineral density, trabecular area, total area, cortical thickness by custom software were comparable, but for CTh_Stratec, Tb.Sp, BV/TV, and CDen, the differences between imaging devices varied with magnitude of the estimate. We recommend that researchers or clinicians interested in using pQCT to measure apparent trabecular structure or cortical thickness at the epiphyses, or in comparing findings from different devices, be aware of the differences between HR-pQCT and pQCT.     

Comparative bone status assessment by dual energy X-ray absorptiometry, peripheral quantitative computed tomography and quantitative ultrasound in adolescents and young adults with cystic fibrosis

PurposeQuantitative ultrasound bone sonometry (QUS) might be a promising screening method for cystic fibrosis (CF)-related bone disease, given its absence of radiation exposure, portability of the equipment and low cost.The value of axial transmission forearm QUS in detecting osteopenia in CF was therefore studied.MethodsWe investigated the application of QUS in the evaluation of bone status in a group of 64 adolescents (> 12 years) and young adults (< 40 years) with CF in a comparison with a dual X-ray absorptiometry (DXA) of the whole body and peripheral quantitative computed tomography (pQCT) of the radius at 4% and 66% sites.ResultsMean (SD) Z-scores of speed of sound (SOS), whole body bone mineral content (BMC), radial trabecular bone mineral density (BMD), and radial cortical BMD were respectively − 0.31 (0.78), − 0.09 (1.28), 0.10 (1.16) and − 0.62 (2.88). The pQCT determined bone geometry values (cortical bone area and cortical thickness) were more depressed than the BMD data. QUS had a sensitivity and specificity of respectively 0% and 96% for diagnosing osteopenia (based on a whole body BMC Z-score < − 2).ConclusionsQUS cannot replace DXA, but can screen out patients with normal bone mass. Further and larger studies are needed to examine if QUS may reflect other aspects than bone mass, or if it is possible to improve its sensitivity by supplementing the SOS results with clinical risk factors.     

Relationship between the duration of paralysis and bone structure: a pQCT study of spinal cord injured individuals

The aim of the present study was to describe bone loss of the separate compartments of trabecular and cortical bone, as well as changes in bone geometry of a large number of spinal cord injured (SCI) individuals. Eighty-nine motor complete spinal cord injured men (24 tetraplegics and 65 paraplegics) with a duration of paralysis of between 2 months and 50 years were included in the study. Distal epiphyses and midshafts of the femur, tibia, and radius were measured by peripheral quantitative computed tomography. The same measurements were performed in a reference group of 21 healthy able-bodied men of the same age range. In the femur and tibia, bone mass, total and trabecular bone mineral density (BMDtot and BMDtrab, respectively) of the epiphyses, as well as bone mass and cortical cross-sectional area of the diaphyses, showed an exponential decrease with time after injury in the spinal cord injured subjects. The decreasing bone parameters reached new steady states after 3-8 years, depending on the parameter. Bone mass loss in the epiphyses was approximately 50% in the femur and 60% in the tibia, while the shafts lost only approximately 35% in the femur and 25% in the tibia. In the epiphyses, bone mass was lost by reducing BMD, while in the shaft bone mass was lost by reducing cortical wall thickness, a process achieved by endosteal resorption advancing at a rate of about 0.25 mm/year within the first 5-7 years after injury. Except for a slight transient decrease in cortical BMD of the femoral and tibial shaft during the first 5 years after the spinal cord lesion, cortical BMD of the spinal cord injured subjects was found to be at reference values. Bone parameters of the radial epiphysis in paraplegic subjects showed no deficits compared to the reference group. Furthermore, a trend for an increased radial shaft diameter suggests periosteal apposition as a consequence of increased loading of the arms.     

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.     

Age and sex differences in tibia morphology in healthy adult Caucasians

Variability in peripheral Quantitative Computed Tomography (pQCT) measurement sites limits direct comparisons of results between studies. Further, it is unclear what estimates of bone strength are most indicative of changes due to aging, disease, or interventions. The purpose of this study was to examine age group and sex differences in tibia morphology. Additional purposes of this study were to determine which tibia site or sites are most sensitive for detecting age and sex differences.MethodsSelf-identifying Caucasian men (n = 55) and women (n = 59) ages 20–59 years and separated by decades had their non-dominant tibias measured with pQCT (Stratec XCT 3000) at every 10% of the limb length from 5% to 85% (distal to proximal). Volumetric BMD and BMC of the total, cortical and trabecular bone were determined, as well as periosteal (PeriC) and endosteal (EndoC) circumferences, and cortical thickness (CTh).ResultsThere were significant (p < 0.01) site effects for all BMC, vBMD, PeriC and EndoC measures. Large sex differences (men > women) in Tot.BMC (21–28%) were paralleled by differences in Cort.BMC (21–25%) (p < 0.01). Site 1 sex interaction effects were significant (p < 0.05) for BMC (peak sex difference: 5%, 15%, 25%, 85% sites) and circumference (peak sex difference: 65% site) variables. CTh and total vBMD were lowest (p < 0.05) in 50–59 year group, and EndoC was highest in the 50–59 year group. Site 1 age interactions existed for Cort.vBMD, Tot.BMC (85% site), and EndoC (25%, 35%, 55%–85% sites). Correcting for bone free lean body mass (BFLBM) greatly reduced sex differences, eliminating sex 1 site interaction effects, but sex main effects remained significant. Correcting for BFLBM did not eliminate age effects.ConclusionThe magnitude of age and sex differences in tibia variables varied by measurement site demonstrating the need for standardization of measurement sites.     

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.     

Effects of 16-month treatment with the cathepsin K inhibitor ONO-5334 on bone markers,mineral density,strength and histomorphometry in ovariectomized cynomolgus monkeys

We examined the effects of ONO-5334, a cathepsin K inhibitor, on bone markers, BMD, strength and histomorphometry in ovariectomized (OVX) cynomolgus monkeys. ONO-5334 (1.2, 6 and 30 mg/kg/day, p.o.), alendronate (0.05 mg/kg/2 weeks, i.v.), or vehicle was administered to OVX monkeys (all groups N = 20) for 16 months. A concurrent Sham group (N = 20) was also treated with vehicle for 16 months. OVX significantly increased bone resorption and formation markers and decreased BMD in lumbar vertebra, femoral neck, proximal tibia and distal radius. Alendronate suppressed these parameters to a level similar to that in the Sham-operated monkeys. ONO-5334 at doses 6 and 30 mg/kg decreased bone resorption markers to a level roughly half of that in the Sham group, while keeping bone formation markers level above that in the Sham monkeys. Changes in DXA BMD confirmed that ONO-5334 at doses 6 and 30 mg/kg increased BMD to a level greater than that in the Sham group in all examined sites. In the proximal tibia, in vivo pQCT analysis showed that ONO-5334 at doses 6 and 30 mg/kg suppressed trabecular BMD loss to the sham level. However, ONO-5334 increased cortical BMD, cortical area and cortical thickness to a level greater than that in the Sham group, suggesting that ONO-5334 improves both cortical BMD and cortical geometry. Histomorphometric analysis revealed that ONO-5334 suppressed bone formation rate (BFR) at osteonal site in the midshaft femur but did not influence OVX-induced increase in BFR at either the periosteal or endocortical surfaces. Unlike alendronate, ONO-5334 increased osteoclasts surface (Oc.S/BS) and serum tartrate-resistant acid phosphatise 5b (TRAP5b) activity, highlighting the difference in the mode of action between these two drugs. Our results suggest that ONO-5334 has therapeutic potential not only in vertebral bones, but also in non-vertebral bones.     

The high bone mass phenotype is characterised by a combined cortical and trabecular bone phenotype: Findings from a pQCT case–control study

High bone mass (HBM), detected in 0.2% of DXA scans, is characterised by a mild skeletal dysplasia largely unexplained by known genetic mutations. We conducted the first systematic assessment of the skeletal phenotype in unexplained HBM using pQCT in our unique HBM population identified from screening routine UK NHS DXA scans.pQCT measurements from the mid and distal tibia and radius in 98 HBM cases were compared with (i) 65 family controls (constituting unaffected relatives and spouses), and (ii) 692 general population controls.HBM cases had substantially greater trabecular density at the distal tibia (340 [320, 359] mg/cm³), compared to both family (294 [276, 312]) and population controls (290 [281, 299]) (p < 0.001 for both, adjusted for age, gender, weight, height, alcohol, smoking, malignancy, menopause, steroid and estrogen replacement use). Similar results were obtained at the distal radius. Greater cortical bone mineral density (cBMD) was observed in HBM cases, both at the midtibia and radius (adjusted p < 0.001). Total bone area (TBA) was higher in HBM cases, at the distal and mid tibia and radius (adjusted p < 0.05 versus family controls), suggesting greater periosteal apposition. Cortical thickness was increased at the mid tibia and radius (adjusted p < 0.001), implying reduced endosteal expansion. Together, these changes resulted in greater predicted cortical strength (strength strain index [SSI]) in both tibia and radius (p < 0.001). We then examined relationships with age; tibial cBMD remained constant with increasing age amongst HBM cases (adjusted β ? 0.01 [? 0.02, 0.01], p = 0.41), but declined in family controls (? 0.05 [? 0.03, ? 0.07], p < 0.001) interaction p = 0.002; age-related changes in tibial trabecular BMD, CBA and SSI were also divergent. In contrast, at the radius HBM cases and controls showed parallel age-related declines in cBMD and trabecular BMD.HBM is characterised by increased trabecular BMD and by alterations in cortical bone density and structure, leading to substantial increments in predicted cortical bone strength. In contrast to the radius, neither trabecular nor cortical BMD declined with age in the tibia of HBM cases, suggesting attenuation of age-related bone loss in weight-bearing limbs contributes to the observed bone phenotype.     

Evidence for Enhanced Characterization of Cortical Bone Using Novel pQCT Shape Software

Bone shape, mass, structural geometry, and material properties determine bone strength. This study describes novel software that uses peripheral quantitative computed tomography (pQCT) images to quantify cortical bone shape and investigates whether the combination of shape-sensitive and manufacturer's software enhances the characterization of tibiae from contrasting populations. Existing tibial pQCT scans (4% and 50% sites) from Gambian (n = 38) and British (n = 38) women were used. Bone mass, cross-sectional area (CSA), and geometry were determined using manufacturer's software; cross-sectional shape was quantified using shape-sensitive software. At 4% site, Gambian women had lower total bone mineral content (BMC: ?15.4%), CSA (?13.4%), and trabecular bone mineral density (BMD: ?19%), but higher cortical subcortical BMD (6.1%). At 50% site, Gambian women had lower cortical BMC (?7.6%), cortical CSA (?12.6%), and mean cortical thickness (?15.0%), but higher cortical BMD (4.9%) and endosteal circumference (8.0%). Shape-sensitive software supported the finding that Gambian women had larger tibial endosteal circumference (9.8%), thinner mean cortical thickness (?26.5%) but smaller periosteal circumference (?5.6%). Shape-sensitive software revealed that Gambian women had tibiae with shorter maximum width (?7.6%) and thinner cortices (?22% to ?41.2%) and more closely resembled a circle or ellipse. Significant differences remained after adjusting for age, height, and weight. In conclusion, shape-sensitive software enhanced the characterization of tibiae in 2 contrasting groups of women.     

History of amenorrhoea compromises some of the exercise-induced benefits in cortical and trabecular bone in the peripheral and axial skeleton: A study in retired elite gymnasts

BackgroundFemale gymnasts frequently present with overt signs of hypoestrogenism, such as late menarche or menstrual dysfunction. The objective was to investigate the impact of history of amenorrhoea on the exercise-induced skeletal benefits in bone geometry and volumetric density in retired elite gymnasts.Subjects and methods24 retired artistic gymnasts, aged 17–36 years, who had been training for at least 15 h/week at the peak of their career and had been retired for 3–18 years were recruited. They had not been engaged in more than 2 h/week of regular physical activity since retirement. Former gymnasts who reported history of amenorrhoea (‘AME’, n = 12: either primary or secondary amenorrhoea) were compared with former gymnasts (‘NO-AME’, n = 12) and controls (‘C’, n = 26) who did not report history of amenorrhoea. Bone mineral content (BMC), total bone area (ToA) and total volumetric density (ToD) were measured by pQCT at the radius and tibia (4% and 66%). Trabecular volumetric density (TrD) and bone strength index (BSI) were measured at the 4% sites. Cortical area (CoA), cortical thickness (CoTh), medullary area (MedA), cortical volumetric density (CoD), stress–strain index (SSI) and muscle and fat area were measured at the 66% sites. Spinal BMC, areal BMD and bone mineral apparent density (BMAD) were measured by DXA.ResultsMenarcheal age was delayed in AME when compared to NO-AME (16.4 ± 0.5 years vs. 13.3 ± 0.4 years, p < 0.001). No differences were detected between AME and C for height-adjusted spinal BMC, aBMD and BMAD, TrD and BSI at the distal radius and tibia, CoA at the proximal radius, whereas these parameters were greater in NO-AME than C (p < 0.05–0.005). AME had lower TrD and BSI at the distal radius, and lower spinal BMAD than NO-AME (p < 0.05) but they had greater ToA at the distal radius (p < 0.05).ConclusionGreater spinal BMC, aBMD and BMAD as well as trabecular volumetric density and bone strength in the peripheral skeleton were found in former gymnasts without a history of menstrual dysfunction but not in those who reported either primary or secondary amenorrhoea. History of amenorrhoea may have compromised some of the skeletal benefits associated with high-impact gymnastics training.     

Improvements in hip trabecular,subcortical, and cortical density and mass in postmenopausal women with osteoporosis treated with denosumab

In the FREEDOM study, denosumab treatment (60 mg every 6 months) decreased bone resorption, increased bone mineral density (BMD), and reduced new vertebral, nonvertebral, and hip fractures over 36 months in postmenopausal women with osteoporosis. In a subset of these women, hip quantitative computed tomography (QCT) was performed at baseline and months 12, 24, and 36. These scans were analyzed using Medical Image Analysis Framework (MIAF) software, which allowed assessment of total hip integral, trabecular, subcortical, and cortical compartments; the cortical compartment was further divided into 2 areas of interest (outer and inner cortex). This substudy reports changes in BMD and bone mineral content (BMC) from baseline and compared placebo with denosumab over 36 months of treatment (placebo N = 26; denosumab N = 36). Denosumab treatment resulted in significant improvements in total hip integral volumetric BMD (vBMD) and BMC from baseline at each time point. At month 36, the mean percentage increase from baseline in total hip integral vBMD and BMC was 6.4% and 4.8%, respectively (both p < 0.0001). These gains were accounted for by significant increases in vBMD and BMC in the trabecular, subcortical, and cortical compartments. In the placebo group, total hip integral vBMD and BMC decreased at month 36 from baseline by − 1.5% and − 2.6%, respectively (both p < 0.05). The differences between denosumab and placebo were also significant at months 12, 24, and 36 for integral, trabecular, subcortical, and cortical vBMD and BMC (all p < 0.05 to < 0.0001). While the largest percentage differences occurred in trabecular vBMD and BMC, the largest absolute differences occurred in cortical vBMD and BMC. In summary, denosumab significantly improved both vBMD and BMC from baseline and placebo, assessed by QCT MIAF, in the integral, trabecular, subcortical, and cortical hip compartments, all of which are relevant to bone strength.     

Quantitative computed tomography (QCT) of the forearm using general purpose spiral whole-body CT scanners: Accuracy,precision and comparison with dual-energy X-ray absorptiometry (DXA)

BackgroundDual-energy X-ray absorptiometry (DXA) allows clinically relevant measurement of bone mineral density (BMD) at central and appendicular skeletal sites, but DXA has a limited ability to assess bone geometry and cannot distinguish between the cortical and trabecular bone compartments. Quantitative computed tomography (QCT) can supplement DXA by enabling geometric and compartmental bone assessments. Whole-body spiral CT scanners are widely available and require only seconds per scan, in contrast to peripheral QCT scanners, which have restricted availability, limited spatial resolution, and require several minutes of scanning time.This study evaluated the accuracy and precision of whole-body spiral CT scanners for quantitatively assessing the distal radius, a common site of non-vertebral osteoporosis-related fractures, and compared the CT-measured densitometric values with those obtained from dual-energy-X-ray absorptiometry.Subjects and methodsA total of 161 postmenopausal women with baseline lumbar spine BMD T-scores between ? 1.0 and ? 2.5 underwent left forearm QCT using whole-body spiral CT scanners twice, 1 month apart. QCT volumes of interest were defined and analyzed at 3 specific radial regions: the ultradistal region by using slices at 8, 9, and 10 mm proximal to the ulnar styloid tip; the distal region by a slice 20 mm proximal; and the middle region by a slice 40 mm proximal. BMD, bone mineral content (BMC), volume, and average cortical thickness and circumference were measured. We evaluated QCT accuracy and precision and also report correlations between QCT and DXA for BMD and BMC.ResultsOverall accuracy and precision errors for BMD, BMC and volume were consistent with known skeletal QCT technology precision and were generally less than 3%. BMD and BMC assessed by QCT and DXA were correlated (r = 0.55 to 0.80).DiscussionWhole-body spiral CT scanners allow densitometric evaluations of the distal radius with good accuracy and very good precision. This original and convenient method provides a tool to further investigate cortical and trabecular bone variables in the peripheral skeleton in osteoporotic patients. These assessments, coupled with evaluation of the effects on cortical and trabecular bone measured in response to therapies for osteoporosis, may advance our understanding of the contributors to non-vertebral fracture occurrence.     

Fractures on bisphosphonates in osteoporosis pseudoglioma syndrome (OPPG): pQCT shows poor bone density and structure

Osteoporosis pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder of childhood osteoporosis and blindness due to inactivating mutations in LDL receptor-like protein 5 (LRP5). We and others have reported improvement in areal bone mineral density (aBMD) by DXA in OPPG on short term bisphosphonates. Long-term data on bisphosphonate use in OPPG and measures of volumetric BMD (vBMD) and cortical structure are not available. In addition, no long-term DXA data on untreated OPPG is available. The aims of this study were to: (1) record low trauma fractures and longitudinal aBMD by DXA in 5 OPPG patients on chronic bisphosphonate treatment, and in 4 OPPG patients never treated (2) to perform tibia peripheral quantitative CT (pQCT) to evaluate volumetric bone mineral density (vBMD), cortical structure and calf muscle area in 6 OPPG patients and 14 unaffected first degree family members. pQCT results were converted to sex-specific Z-scores for age and adjusted for tibia length based on data in > 700 reference participants. We observed 4 fractures (3 femoral shafts) in 3 OPPG patients while on bisphosphonates, after each achieved significant improvement in aBMD. OPPG participants had significantly lower mean trabecular vBMD (− 1.51 vs. 0.17, p = 0.002), cortical area (− 2.36 vs. 0.37; p < 0.001) and periosteal circumference (− 1.86 vs. − 0.31, p = 0.001) Z-scores, compared with unaffected participants and had a trend toward lower muscle area Z-score (− 0.69 vs. 0.47, p = 0.12). These data demonstrate substantial bone fragility despite improvements in aBMD. The pQCT data provide insight into the fragility with substantial deficits in trabecular vBMD and cortical dimensions, consistent with OPPG effects of bone formation. Treatment that improves bone quality is needed to reduce fractures in OPPG.     

Bone mineral density in upper and lower extremities during 12 months after spinal cord injury measured by peripheral quantitative computed tomography

OBJECTIVE: To evaluate the loss of trabecular and cortical bone mineral density in radius, ulna and tibia of spinal cord injured persons with different levels of neurologic lesion after 6, 12 and 24 months of spinal cord injury (SCI). DESIGN: Prospective study in a Paraplegic Centre of the University Hospital Balgrist, Zurich. SUBJECTS AND METHODS: Twenty-nine patients (27 males, two females) were examined by the highly precise peripheral quantitative computed tomography (pQCT) soon after injury and subsequently at 6, 12 and in some cases 24 months after SCI. Using analysis of the bone mineral density (BMD), various degrees of trabecular and cortical bone loss were recognised. A rehabilitation program was started as soon as possible (1-4 weeks) after SCI. The influence of the level of neurological lesion was determined by analysis of variance (ANOVA). Spasticity was assessed by the Ashworth Scale. RESULTS: The trabecular bone mineral density of radius and ulna was significantly reduced in subjects with tetraplegia 6 months (radius 19% less, P<0.01; ulna 6% less, P>0.05) and 12 months after SCI (radius 28% less, P<0.01; ulna 15% less, P<0.05). The cortical bone density was significantly reduced 12 months after SCI (radius 3% less, P<0.05; ulna 4% less, P<0.05). No changes in BMD of trabecular or cortical bone of radius and ulna were detected in subjects with paraplegia. The trabecular BMD of tibia was significantly reduced 6 months (5% less, P<0.05) and 12 months after SCI (15% less, P<0.05) in all subjects with SCI. The cortical bone density of the tibia only was decreased after a year following SCI (7% less, P<0.05). No significant difference between both groups, subjects with paraplegia and subjects with tetraplegia was found for tibia cortical or trabecular BMD. There was no significant influence for the physical activity level or the degree of spasticity on bone mineral density in all subjects with SCI. CONCLUSIONS: Twelve months after SCI a significant decrease of BMD was found in trabecular bone in radius and in tibia of subjects with tetraplegia. In subjects paraplegia, a decrease only in tibia BMD occurred. Intensity of physical activity did not significantly influence the loss of BMD in all subjects with para- and tetraplegia. However, in some subjects regular intensive loading exercise activity in early rehabilitation (tilt table, standing) can possibly attenuate the decrease of BMD of tibia. No influence was found for the degree of spasticity on the bone loss in all subjects with SCI.     

Reduced physical activity corresponds with greater bone loss at the trabecular than the cortical bone sites in men

Previous research has been inconclusive as to whether high peak bone mineral density (BMD, g/cm²) resulting from previous physical activity is retained with reduced activity later in life. The aim of this 12-year longitudinal study was to investigate the association between BMD loss and reduced physical activity (h/wk) at trabecular and cortical bone sites in men. Three groups with a mean age of 17 years at baseline were investigated: i) 51 athletes who discontinued their active careers during the follow-up period (former athletes), ii) 16 athletes who were active throughout the follow-up period (active athletes), and iii) 25 controls. BMD loss at the hip, spine, and pelvis (mainly trabecular bone) was compared to BMD loss at femur, humerus, and legs (mainly cortical bone) during a 12-year follow-up period. Across the total follow-up period in the total cohort, reduced physical activity was more strongly associated with changes at trabecular BMD sites, i.e. hip, spine, and pelvis (B = 0.008–0.005 g/cm² per weekly hour physical activity (h), p < 0.001), than at cortical bone sites, i.e. humerus, legs (B = 0.002–0.003 g/cm²/h, p < 0.05), and femur (p > 0.05). At the final follow-up, former athletes showed higher BMD than controls only at the cortical bone sites of the humerus, legs, and femur (difference 0.05–0.10 g/cm², p < 0.05). In conclusion, this study indicates that predominantly trabecular bone is lost with reduced physical activity levels in young men. Benefits were still evident at the more cortical sites eight years after the discontinuation of an active sports career.     

Longitudinal changes in lean mass predict pQCT measures of tibial geometry and mineralisation at 6–7 years

BackgroundStudies in childhood suggest that both body composition and early postnatal growth are associated with bone mineral density (BMD). However, little is known of the relationships between longitudinal changes in fat (FM) and lean mass (LM) and bone development in pre-pubertal children. We therefore investigated these associations in a population-based mother-offspring cohort, the Southampton Women's Survey.MethodsTotal FM and LM were assessed at birth and 6–7 years of age by dual-energy x-ray absorptiometry (DXA). At 6–7 years, total cross-sectional area (CSA) and trabecular volumetric BMD (vBMD) at the 4% site (metaphysis) of the tibia was assessed using peripheral quantitative computed tomography [pQCT (Stratec XCT-2000)]. Total CSA, cortical CSA, cortical vBMD and strength–strain index (SSI) were measured at the 38% site (diaphysis). FM, LM and bone parameters were adjusted for age and sex and standardised to create within-cohort z-scores. Change in LM (ΔLM) or FM (ΔFM) was represented by change in z-score from birth to 7 years old and conditioned on the birth measurement. Linear regression was used to explore the associations between ΔLM or ΔFM and standardised pQCT outcomes, before and after mutual adjustment and for linear growth. The β-coefficient represents SD change in outcome per unit SD change in predictor.ResultsDXA at birth, in addition to both DXA and pQCT scans at 6–7 years, were available for 200 children (48.5% male). ΔLM adjusted for ΔFM was positively associated with tibial total CSA at both the 4% (β = 0.57SD/SD, p < 0.001) and 38% sites (β = 0.53SD/SD, p < 0.001), cortical CSA (β = 0.48SD/SD, p < 0.001) and trabecular vBMD (β = 0.30SD/SD, p < 0.001), but not with cortical vBMD. These relationships persisted after adjustment for linear growth. In contrast, ΔFM adjusted for ΔLM was only associated with 38% total and cortical CSA, which became non-significant after adjustment for linear growth.ConclusionIn this study, gain in childhood LM was positively associated with bone size and trabecular vBMD at 6–7 years of age. In contrast, no relationships between change in FM and bone were observed, suggesting that muscle growth, rather than accrual of fat mass, may be a more important determinant of childhood bone development.     

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.     

Muscle volume is related to trabecular and cortical bone architecture in typically developing children

IntroductionMuscle is strongly related to cortical bone architecture in children; however, the relationship between muscle volume and trabecular bone architecture is poorly studied. The aim of this study was to determine if muscle volume is related to trabecular bone architecture in children and if the relationship is different than the relationship between muscle volume and cortical bone architecture.Materials and methodsForty typically developing children (20 boys and 20 girls; 6 to 12 y) were included in the study. Measures of trabecular bone architecture [i.e., apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp)] in the distal femur, cortical bone architecture [cortical volume, total volume, section modulus (Z) and polar moment of inertia (J)] in the midfemur, muscle volume in the midthigh and femur length were assessed using magnetic resonance imaging. Total physical activity and moderate-to-vigorous physical activity were assessed using an accelerometer-based activity monitor worn around the waist for four days. Calcium intake was assessed using diet records. Relationships among the measures were tested using multiple linear regression analysis.ResultsMuscle volume was moderately-to-strongly related to measures of trabecular bone architecture [appBV/TV (r = 0.81), appTb.N (r = 0.53), appTb.Th (r = 0.67), appTb.Sp (r = − 0.71); all p < 0.001] but more strongly related to measures of cortical bone architecture [cortical volume (r = 0.96), total volume (r = 0.94), Z (r = 0.94) and J (r = 0.92; all p < 0.001)]. Similar relationships were observed between femur length and measures of trabecular (p < 0.01) and cortical (p < 0.001) bone architecture. Sex, physical activity and calcium intake were not related to any measure of bone architecture (p > 0.05). Because muscle volume and femur length were strongly related (r = 0.91, p < 0.001), muscle volume was scaled for femur length (muscle volume/femur length^2.77). When muscle volume/femur length^2.77 was included in a regression model with femur length, sex, physical activity and calcium intake, muscle volume/femur length^2.77 was a significant predictor of appBV/TV, appTb.Th and appTb.Sp (partial r = 0.44 to 0.49, p < 0.05) and all measures of cortical bone architecture (partial r = 0.47 to 0.54; p < 0.01).ConclusionsThe findings suggest that muscle volume in the midthigh is related to trabecular bone architecture in the distal femur of typically developing children. The relationship is weaker than the relationship between muscle volume in the midthigh and cortical bone architecture in the midfemur, but the discrepancy is driven, in large part, by the greater dependence of cortical bone architecture measures on femur length.     

应用pQCT与DXA定量检测去卵巢大鼠股骨近端骨质疏松建模效果的对比研究

目的比较pQCT与DXA定量检测去卵巢大鼠股骨近端骨质疏松的建模效果的能力。方法16只8月龄Wistar雌性大鼠(平均体重350g)随机分为模型组(卵巢切除组)与对照组(卵巢假切除组)。术后3个月,取大鼠左侧股骨。应用肢体计算机断层扫描(pQCT)与双能X线骨密度仪(DXA)对骨质疏松建模效果进行对比研究:(1)确定pQCT与DXA测量精度,即计算重复测量的精度误差;(2)比较应用两种骨密度仪所测得的对照组、模型组的骨密度、骨矿含量、骨几何结构参数及其相关系数。结果(1)pQCT总骨及松质骨体密度的测量精度误差分别为2.27%与2.00%,而DXA骨面密度的测量精度误差为3.36%。(2)模型组pQCT总骨体密度和松质骨体密度分别低于对照组8.2%和15.0%犤(模型组-对照组)/对照组×100%犦,差异有显著性(P<0.01);而模型组DXA骨面密度低于对照组3.0%,差异无显著性(P>0.05)。模型组pQCT总骨骨矿含量低于对照组3.7%,差异无显著性(P>0.05),而松质骨骨矿含量低于对照组11.4%,差异有显著性(P<0.05);模型组DXA骨矿含量低于对照组3.0%,差异无显著性(P>0.05)。(3)DXA骨矿含量与pQCT总骨骨矿含量之间呈正相关(r=0.82,P<0.001);DXA骨投影面积与pQCT骨体积之间亦呈正相关(r=0.52,P<0.05);DXA骨面密度与pQCT总骨体密度之间无相关关系(r=0.14,P>0.05)。DXA     

Trabecular and cortical bone deficits are present in children and adolescents with cystic fibrosis

Osteopenia and increased fracture rates are well-recognized in adults with CF, but neither the specific contributions of cortical and trabecular bone deficits to bone fragility nor their presence in youth with CF are well-characterized. This study sought to characterize cortical and trabecular volumetric bone mineral density (vBMD), geometry, and biomechanical competence in children with CF and determine their relationship to growth, body composition, and disease severity. Peripheral quantitative computerized tomography (pQCT) measures of total, cortical, and trabecular vBMD, cortical, muscle, and fat cross-sectional areas (CSA), periosteal and endosteal circumferences, and the polar unweighted section modulus (Zp) of the tibia were converted to age- and tibial length-adjusted Z-scores in 97 CF and 199 healthy children (aged 8–21 y). Effects of body composition and pulmonary function (forced expiratory volume in 1 s, FEV1) upon pQCT outcomes were determined using linear regression. Children with CF (FEV₁%-predicted: 84.4 + 19.7) had lower weight-, height-, BMI-, and whole body lean mass (LBM)-Z and tibial length. Females with CF had lower (p < 0.01) total and trabecular vBMD; cortical, muscle, and fat CSA; Zp and periosteal circumference than females in the healthy reference group. These bone differences persisted after adjustment for BMI-Z and to a great extent following adjustment for muscle CSA. Males with CF had lower (p < 0.01) cortical, muscle, and fat CSA and their trabecular vBMD deficit approached significance (p = 0.069). Deficits were attenuated by adjustment for BMI-Z and to a greater extent adjustment for muscle CSA-Z. The relationship between FEV1%-predicted and pQCT outcomes persisted only in males following adjustment for age and BMI-Z. The CF cohort had lower tibial muscle CSA than expected for their LBM. In this relatively healthy, young CF cohort, deficits in trabecular and multiple cortical bone parameters were present. In females, deficits were greater at older ages and were not fully explained by alterations in body composition. In males worsening pulmonary function was associated with greater deficits that was not explained by increasing age or compromised nutritional status. The occurrence of these differences in CF youth highlights the importance of instituting measures to optimize peak bone mass early in the course of CF.