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Biomedical subjects

J Aerssens

Publications and source records attributed to J Aerssens.

At least 19 recordsLinked to original sources

Validation of 16S rDNA sequencing in microdissected bowel biopsies from Crohn's disease patients to assess bacterial flora diversity.

The bowel flora is implicated in Crohn's disease (CD) pathogenesis but its precise role is still unclear. Several non-mutually exclusive hypotheses have been proposed: an unidentified persistent pathogen; excessive bacterial translocation; an immune system abnormality in response to normal bacteria; or a breakdown in the balance between protective and harmful bacteria. These hypotheses can be tested by identifying bacteria in specific microscopic bowel structures or lesions. The present paper describes a novel technique to assess bacterial flora diversity in bowel biopsies, by combining laser capture microdissection with broad-range 16S rDNA sequencing. Fifty-four samples comprising histologically normal and pathological mucosa, MALT, ulcers, submucosal lymphangiectasias, epithelioid granulomas, and lymph nodes were microdissected out of 30 bowel biopsies from five CD patients. Bacterial 16S rDNA was successfully amplified by PCR in all samples, and PCR products from 15 samples were selected for cloning and sequence analysis. A total of 729 bacterial DNA sequences were analysed, which could be attributed to six different phyla (Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria, and Planctomycetes). DNA from typical bowel bacteria (Enterobacteriaceae, Clostridiales, Bacteroidetes, Fusobacteria) was detected in all microdissected areas. It was thus convincingly demonstrated that 16S rDNA sequencing can be combined with microdissection to study the bowel flora. However, no specific persistent pathogen causal for CD was identified. The results suggest that Enterobacteriaceae may initiate or colonize ulcers in CD. Translocation of bacteria through established mucosal lesions or as a result of increased permeability may be involved in the evolution towards chronic inflammation and in the establishment of persistent lesions. Further study is needed to confirm these preliminary findings.

Adolescent↗

Quantitative trait loci for human muscle strength: linkage analysis of myostatin pathway genes.

This study reports the results of a multipoint linkage study that aims to unravel the genetic basis of muscle strength and muscle mass in humans. Myostatin (GDF8) is known to be a strong inhibitor of muscle growth in animals. However, studies examining human myostatin polymorphisms are rare and are limited to the GDF8 gene itself. Here, the contribution to isometric and concentric knee strength of nine key proteins involved in the myostatin pathway is studied in a nonparametric multipoint linkage analysis by means of a variance components and regression method. A sample of 367 healthy young male siblings was phenotyped on an isokinetic dynamometer and genotyped for markers of the myostatin pathway genes. Three of the loci were found significantly linked with a quantitative trait locus (QTL) for knee muscle strength. First, D13S1303 showed replication of an explorative single-point linkage study with a maximum LOD score of 2.7 (P = 0.0002). Second, maximum LOD scores of 3.4 (P = 0.00004) and 3.3 (P = 0.00005) were observed for markers D12S1042 and D12S85, respectively, at 12q12-14. Finally, marker D12S78 showed an LOD score of 2.7 at 12q22-23. We conclude that several genes involved in the myostatin pathway, but not the myostatin gene itself, are important QTLs for human muscle strength. An additional set of valuable candidate genes that were not part of the myostatin pathway was found in the chromosome 12 and 13 genomic regions.

Adolescent↗

Linkage of myostatin pathway genes with knee strength in humans.

This study was the first to explore the potential role of the myostatin (GDF8) pathway in relation to muscle strength and estimated muscle cross-sectional area in humans using linkage analysis with a candidate gene approach. In young male sibs (n = 329) 11 polymorphic markers in or near 10 candidate genes from the myostatin pathway were genotyped. Muscle mass was estimated by anthropometric measurements, and maximal knee strength was evaluated using isokinetic dynamometers (Cybex NORM). Single-point nonparametric variance components and linear quantitative trait locus regression linkage analysis methods were used. Linkage patterns were observed between knee extension and flexion peak torque with markers D2S118 (GDF8), D6S1051 (CDKN1A), and D11S4138 (MYOD1), and a maximum LOD score of 2.63 (P = 0.0002) was observed with D2S118. The ratios of peak torque over muscle and bone area of the midthigh of the lower contraction velocity (60 degrees/s) showed more frequently significant LOD scores than the torques at high velocity (240 degrees/s). Although myostatin is physiologically more related to muscle mass through possible effects of hyperplasia and hypertrophy than it is to strength, only two estimated muscle cross-sectional areas were marginally linked (LOD 1.06 and 1.07, P = 0.01) with marker D2S118 near GDF8 (2q32.2). The present results gave suggestive evidence that the myostatin pathway might be important for strength phenotypes, and GDF8, CDKN1A, and MYOD1 are potential candidate regions for a further and denser mapping with respect to these phenotypes.

Adolescent↗

Polymorphisms of the VDR, ER and COLIA1 genes and osteoporotic hip fracture in elderly postmenopausal women.

In view of the reported associations between osteoporosis and polymorphisms of the vitamin D receptor (VDR), collagen Ialpha1 (COLIA1) and estrogen receptor (ER) genes, an association study was performed between VDR, COLLIA1, and ER genotypes and bone mineral density, biochemical markers of bone turnover and hip fracture occurrence in Belgian older postmenopausal women. The gene polymorphisms were evaluated by restriction fragment length polymorphism analyses, using the restriction enzymes BsmI (VDR), AccB7I (COLIA1), and PvuII and XbaI (ER), respectively. As expected, bone mineral density and biochemical analyses demonstrated significant differences between hip fracture patients and elderly controls. However, no significant differences in genotype distributions or allele frequencies were observed between the cases (n = 135, age 78 +/- 9 years) and controls (n = 239, age 76 +/- 4 years) for any of the gene polymorphisms. Stratification of both study populations according to VDR, COLIA1 or ER genotype did not reveal any statistically significant difference in bone density or bone turnover between subgroups with different genotypes. In conclusion, despite its limited statistical power the outcome of this study does not support the hypothesis of a major contribution of the VDR, COLIA1 or ER polymorphisms to explain variations in bone mineral density or bone turnover, or to identify elderly women at risk of osteoporotic hip fracture.

Aged↗

The effect of modifying dietary calcium intake pattern on the circadian rhythm of bone resorption.

In order to assess day-to-day variations of the circadian rhythm of biochemical bone resorption markers, urinary morning (6-8 a.m.) and evening (7-10 p.m.) samples from 35 individuals were monitored during 3 subsequent days. The bone-specific deoxypyridinoline (DPD) crosslinks of type I collagen followed a circadian rhythm in all individuals. In contrast, no such pattern was observed in the urinary hydroxyproline/creatinine and calcium/creatinine measurements. The DPD crosslink measurements showed a much larger difference between the morning and evening samples collected within 1 day compared with the variation between the samples collected in the morning or evening on subsequent days, indicating the importance of adequate timing of urine sampling for clinical trials aiming to monitor effects on bone resorption. The analysis of DPD crosslinks was then used to evaluate the effects of different patterns of dietary calcium intake on the circadian rhythm of bone resorption in osteoporotic patients. No significant effect on the circadian rhythm of the DPD crosslinks was found after concentrating the normal daily calcium intake to the evening (6-10 p.m.) during 8 days (n = 7). Ingestion of a dietary calcium supplement (600 mg) at 10 p.m. during 8 days (n = 7) resulted in an increased urinary calcium excretion in the morning, and a flattening of the circadian peak and nadir concentrations of urinary DPD/creatinine. The absolute levels of DPD/creatinine in the morning and evening urine samples, respectively, were not significantly altered compared with the control day. We conclude that dietary calcium supplementation in the evening only marginally affects the circadian rhythm of urinary DPD crosslinks in established osteoporosis patients.

Aged↗

Down-regulation of the serum stimulatory components of the insulin-like growth factor (IGF) system (IGF-I, IGF-II, IGF binding protein [BP]-3, and IGFBP-5) in age-related (type II) femoral neck osteoporosis.

Both a decrease in bone formation and an increase in bone resorption have been implicated in the pathogenesis of age-related (type II) femoral neck osteoporosis. While the increase in the bone resorption rate has been shown to be partially related to secondary hyperparathyroidism, the mechanisms underlying the decline in bone formation have not yet been identified. The aim of the present study was to test the hypothesis that the bone formation deficit associated with type II osteoporosis might be due to secondary hyperparathyroidism and/or to a deficiency of the insulin-like growth factor (IGF) system. Circulating concentrations of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, 25-hydroxycholecalciferol (25(OH)D3), and intact parathyroid hormone (PTH) were measured in 50 elderly women after sustaining a hip fracture and in 50 healthy age-matched controls. In addition, serum levels of osteocalcin (OC), skeletal alkaline phosphatase, and N-terminal procollagen peptide and urinary pyridinium cross-links were determined as markers of bone remodeling, and bone mineral density (BMD) was assessed at the proximal femur. In the patient group, serum was drawn within 18 h of the fracture and prior to surgery. Circulating protein concentrations did not change over this time frame. No difference was found between mean IGFBP-4 serum levels in the two groups studied, while mean levels of IGF-I, IGF-II, IGFBP-3, IGFBP-5, 25(OH)D3, and markers of bone formation were significantly lower (p < 0.006) in patients as compared with healthy subjects. Serum PTH and urinary pyridinium cross-links, however, were markedly increased (p < 0.001) in the osteoporotic group. In pooled data from the normal and osteoporotic populations, age-adjusted multiple regression models based on IGF-I, IGF-II, IGFBP-3, and IGFBP-5 were found to be highly predictive of serum OC (R2 = 19%, p < 0.001) and BMD of femoral neck (R2 = 49%, p < 0.0001), consistent with an effect of the anabolic IGF components on overall bone formation rate. Similar models based on 25(OH)D3 and PTH, however, were statistically unrelated to OC. To address further the potential impact of trauma on circulating IGF system components, we measured IGF system component levels in 10 male patients within 18 h following tibial fracture and in 10 age-matched normal male subjects. There was no significant difference in serum level of any of the IGF system components between the two groups. Although limited by its cross-sectional design, the present study suggests that, in addition to bone resorption resulting from secondary hyperparathyroidism, impaired bone formation associated with deficiency of the IGF system might predispose elderly women to fragility fracture of the proximal femur.

Age Factors↗

Lack of association between osteoarthritis of the hip and gene polymorphisms of VDR, COL1A1, and COL2A1 in postmenopausal women.

OBJECTIVE: To evaluate whether DNA polymorphisms of the VDR (vitamin D receptor), COL1A1 (alpha1 type I collagen), and COL2A1 (alpha1 type II collagen) genes, which have previously been linked to bone mineral density (BMD) and/or osteoarthritis (OA), are also associated with OA of the hip (OAH). METHODS: Genotype frequency distributions were compared between a group of 239 elderly healthy female controls and a group of 75 female OAH patients who underwent total hip replacement. All participants underwent BMD measurements of the total body, lumbar spine, and femoral neck. Mutation detection was done using polymerase chain reaction followed by restriction enzyme digestion. Polymorphisms were detected by digestion with Bsm I for VDR, Acc B7I for COL1A1, and Pvu II for COL2A1. RESULTS: None of the genotype frequency distributions of any of the examined polymorphisms was significantly different between the OAH group and the control group. No significant differences in BMD variables were observed after stratification of the subjects according to the examined genotypes within each study group. CONCLUSION: In Belgian postmenopausal women, the examined polymorphisms of the candidate genes VDR, COL1A1, and COL2A1 do not significantly contribute to an increased prevalence of OAH or to differences in BMD.

Aged↗

Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone research.

This study compares bone composition, density, and quality in bone samples derived from seven vertebrates that are commonly used in bone research: human, dog, pig, cow, sheep, chicken, and rat. Cortical femoral bone samples were analyzed for their content of ash, collagen, extractable proteins, and insulin-like growth factor-I. These parameters were also measured in bone powder fractions that were obtained after separation of bone particles according to their density. Large interspecies differences were observed in all analyses. Of all species included in the biochemical analyses, rat bone was most different, whereas canine bone best resembled human bone. In addition, bone density and mechanical testing analyses were performed on cylindrical trabecular bone cores. Both analyses demonstrated large interspecies variations. The lowest bone density and fracture stress values were found in the human samples; porcine and canine bone best resembled these samples. The relative contribution of bone density to bone mechanical competence was largely species-dependent. Together, the data reported here suggest that interspecies differences are likely to be found in other clinical and experimental bone parameters and should therefore be considered when choosing an appropriate animal model for bone research.

Adult↗

Distraction bone healing versus osteotomy healing: a comparative biochemical analysis.

This study investigates the biochemical changes in a canine tibia lengthening model in comparison with a nonlengthened osteotomy model. The lengthened and the osteotomized callus and a contralateral corresponding segment were analyzed for their mineralization profile, collagen content, osteocalcin, insulin-like growth factor I (IGF-I), and transforming growth factor beta1 (TGF-beta1). Examinations of bone samples were performed using specimens excised at different time intervals (respectively at 3, 5, 7, 9, and 13 weeks postoperatively). Several serum parameters (alkaline phosphatase [ALP], osteocalcin, IGF-I, and TGF-beta1) were also measured during the experimental period. A progressive increase in mineral parameters was noticed in both the lengthened and the osteotomized areas. A higher level of hydroxyproline and TGF-beta1 was observed in the lengthened area compared with the osteotomized area. IGF-I showed a significant increase in both the lengthened and contralateral control area at the later stage of the experimental period in the lengthened group. In serum, a high level of TGF-beta1 and a progressively increasing osteocalcin concentration were observed in the lengthened dogs in comparison with the osteotomized dogs. Serum ALP was significantly increased in both models during the experimental period. Serum IGF-I was increased in the lengthened models during the distraction period and decreased in the osteotomized models at the early stage of the experimental period. These results suggest that the mechanical strain induced by the Ilizarov distraction procedure stimulates osteoblast proliferation and promotes biosynthesis of bone extracellular matrix in distracted callus. Our data furthermore show that this process is different compared with normal fracture healing.

Alkaline Phosphatase↗

Bone density and local growth factors in generalized osteoarthritis.

Osteoarthritis is usually considered to be a primary disorder of chondrocyte function with secondary changes in bones. However, a defect in the subchondral bone resulting in loss of its shock absorbing capacity could transfer the stress of loading directly to the articular cartilage with secondary changes in the cartilage. Review of histomorphometric and bone densitometric studies at sites of osteoarthritis at the hip or knee revealed that cartilage fibrillation could not be dissociated from bony changes even in the earliest stages of osteoarthritis and that subchondral trabeculae are thickened and more spaced in osteoarthritis. Microfractures of subchondral trabecular bone were less frequently seen in osteoarthritis compared to controls. Changes of the tidemark were found to be multiform and metabolically active in the osteoarthritic process. Endochondral ossification depletes the calcified cartilage at the cartilage/bone interface and the tidemark has been thought of as a calcification front advancing in the direction of non-calcified cartilage. Duplication of the tidemark is cited as evidence of this advancement. In the few experimental animal studies of subchondral bone in osteoarthritis, thicker trabeculae which were closer together were found in guinea pigs already when only mild cartilage changes were present. In the dog, with cruciate ligament transection, changes in bone were later than in the cartilage, but the changes in bone could still contribute to the progression of osteoarthritis. To study if bone changes may precede injury to the cartilage and if metabolic and systemic influences can also alter the subchondral bone, rendering it less able to withstand normal mechanical stresses, bone at different sites in the body has been studied extensively by the authors. Epidemiological and case control studies have revealed that osteoarthritis cases have more bone at all sites than expected and that bone in cases with generalized osteoarthritis shows both quantitative and qualitative differences, including increased contents of growth factors and hypermineralization. These findings suggest that a more generalized bone alteration may be the basis of the pathogenesis of osteoarthritis.

Animals↗

Biochemical and density assessment of the new bone in late remodeling after callus distraction.

Biochemical changes in a canine bone-lengthening model were characterized 5 months after surgery. The mineral content and the total amount of EDTA-extractable noncollagenous proteins, insulin-like growth factor-I, and osteocalcin were determined for the lengthened callus, and a gradient density fractionation analysis of bone powder particles was performed. The results were compared with two other areas of the lengthened tibia and one region of the contralateral tibia. The mineral and osteocalcin contents showed significant decreases, whereas the hydroxyproline concentration was significantly increased. Neither the insulin-like growth factor-I content nor the concentration of EDTA-extractable proteins was significantly different in any of the examined regions.

Animals↗

Factors associated with cortical and trabecular bone loss as quantified by peripheral computed tomography (pQCT) at the ultradistal radius in aging women.

Peripheral quantitative computed tomography (pQCT) allows the separate determination of cortical and trabecular bone mineral density in the peripheral skeleton. This cross-sectional study was designed to examine the effects of healthy aging on pQCT measurements at the ultradistal radius. In a well-defined sample of 129 community-based women, aged 70-87 years, the differences in cortical and trabecular density over the age range were equivalent to losses of -0.41% and -0.65% per year, respectively. To investigate the mechanism of this age-related decline, we assessed relationships between both parameters and height, weight, body mass index, dietary calcium intake, grip strength, and serum concentrations of insulin-like growth factor-I (IGF-I), calcidiol (25(OH)D3), calcitriol (1,25(OH)2D3), parathyroid hormone (PTH), and sex hormone binding globulin (SHBG). Multiple regression was used to adjust for potential confounders. Age was not significant after controlling for other covariables. Body mass index, grip strength, serum IGF-I, 25(OH)D3, and PTH (1-84) were found to be independent predictors of total bone density. Including (total or free) 1,25(OH)2D3 did not improve the model precision. These findings provide evidence that, among other factors, the activity of the growth hormone-IGF-I-axis is of importance for skeletal integrity. Grip strength, serum IGF-I, and PTH (1-84) were discovered to be significantly related to cortical but not to trabecular density, suggesting that different mechanisms may be involved in compact and cancellous bone loss.

Aged↗

Age-associated decline in human femoral neck cortical and trabecular content of insulin-like growth factor I: potential implications for age-related (type II) osteoporotic fracture occurrence.

Recent evidence suggests that regulatory peptides such as insulin-like growth factor-I (IGF-I) are released locally from bone during resorption, and may then act in a sequential manner to regulate the cellular events required for the coupling of bone formation to resorption. Among other factors, a decrease in bone-associated IGF-I levels could therefore result in remodeling imbalance and contribute to the gradual loss of bone that occurs with age. As the femoral neck region is of primary concern for the clinical manifestations of osteoporosis, the current study was intended to assess the IGF-I contents in femoral neck cortical and trabecular bone from aging individuals. Bone samples from the neck region were obtained at postmortem from 39 females and 35 males, aged 23-92 years. Concentrations of IGF-I and osteocalcin were measured by radioimmunoassay in the supernatants obtained after EDTA and guanidine hydrochloride extraction. The total amount of protein present in the extracts was determined by spectrophotometry. IGF-I levels were significantly lower in trabecular compared with cortical bone. Though femoral neck total protein did not vary with donor age, both IGF-I and osteocalcin were found to decline markedly. Between the ages of 23 and 92 years, average yearly rates of loss of 0.30 and 0.21 ng IGF-I/mg protein were observed in cortical and trabecular bone, respectively, corresponding with net losses of nearly 35% of the cortical skeletal content of IGF-I and 41% of the trabecular skeletal content of IGF-I. These changes in bone-associated IGF-I paralleled those of osteocalcin, consistent with an overall decrease in osteoblast function with aging. In women, the rate of decline was significantly faster for trabecular than for cortical IGF-I, however in men, age-dependent changes in cortical and trabecular IGF-I were similar. These findings support the hypothesis that changes in the local IGF regulatory system over time could be a pathophysiologic component of the age-related (type II) femoral neck osteoporotic syndrome.

Adult↗

Determinants of age-associated changes in os calcis ultrasonic indices in elderly women: potential involvement of geriatric hyposomatotropism in bone fragility.

OBJECTIVE: ultrasound measures a clinically relevant property of bone strength in addition to and distinct from bone mass. The aim of the present study was to examine the effects of healthy ageing on ultrasound measurements of the calcaneus. DESIGN: cross-sectional study. STUDY PARTICIPANTS: a sample of 177 community-dwelling healthy women aged 70-87 years. Exclusion criteria were diseases or medications known to affect the musculoskeletal system or the somatotrophic axis. MEASUREMENTS: serum levels of 1,25-dihydroxyvitamin D3 and insulin-like growth factor-I (IGF-I) were measured by radioimmunoassay, serum 25-hydroxyvitamin D3 (25(OH)D3) was determined by competitive binding assay and serum parathyroid hormone was assessed immunochemically. Isometric and isokinetic quadriceps strength were evaluated using a Cybex II system. Calcaneal ultrasound indices--broadband ultrasound attenuation (BUA) and speed of sound (SOS)--were measured with an Achilles system. RESULTS: we found a significant decrease with ageing in BUA and SOS (-0.5 and -1.3% per year, respectively), suggesting a continuing loss of bone quality. Quadriceps strength, serum IGF-I and 25(OH)D3 constituted the best predictors of BUA, while IGF-I was the only parameter found to be independently associated with SOS. CONCLUSION: these findings suggest that, among other factors, the activity of the growth hormone-IGF-I axis is of importance for skeletal integrity. Age-related bone fragility may, in part, be related to geriatric hyposomatotropism.

Aged↗

Calciotropic hormones and markers of bone remodeling in age-related (type II) femoral neck osteoporosis: alterations consistent with secondary hyperparathyroidism-induced bone resorption.

BACKGROUND: Both a decrease in bone formation and the skeletal consequences of secondary hyperparathyroidism have been implied in the pathogenesis of age-related femoral neck osteoporosis. However, studies using biochemical indices of bone remodeling in hip fracture patients have yielded conflicting results. Similarly, secondary hyperparathyroidism has not been a consistent finding in this population. Some of these inconsistencies might reflect differences in the assays used as well as in the timing of the sampling. Moreover, measurements were mostly performed in a limited number of patients. In this regard, the aim of the present study was to analyze potential alterations in bone metabolism in a large population of elderly hip fracture patients. METHODS: Circulating concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D3], intact parathyroid hormone (PTH), and calcitonin were measured in 117 elderly women (within a few hours after sustaining a fracture of the proximal femur) and in 117 healthy age-matched controls. In addition, serum osteocalcin and urinary excretion of (deoxy)pyridinoline were determined as markers of bone formation and resorption, respectively. RESULTS: Serum levels of 25(OH)D and 1,25(OH)2D3 were decreased in hip fracture patients. When correcting for differences in serum vitamin D binding protein, serum 25(OH)D was still significantly lower in patients than in controls, whereas serum 1,25(OH)2D3 was not. Moreover, 25(OH)D deficiency in hip fracture patients was associated with an increase in circulating PTH and urinary excretion of (deoxy)pyridinoline. Serum osteocalcin, on the other hand, was significantly decreased in fracture patients. There was no statistically significant difference in calcitonin. CONCLUSION: These data suggest that there is reduced bone formation and increased bone resorption in patients with hip fracture. Although limited by its cross-sectional design, the present study emphasizes the role of secondary hyperparathyroidism-induced bone resorption in the pathogenesis of age-related osteoporosis, mainly due to a lack of 25(OH)D.

Aged↗

Prediction of vertebral strength in vitro by spinal bone densitometry and calcaneal ultrasound.

Spinal bone mineral density (BMD) measurements and calcaneal ultrasound were compared in terms of their ability to predict the strength of the third lumbar vertebral body using specimens from 62 adult cadavers (28 females, 34 males). BMD was measured using dual X-ray absorptiometry (DXA) in both vertebra and calcaneus. Quantitative computed tomography (QCT) was used to determine trabecular BMD, cortical BMD, cortical area, and total cross-sectional area (CSA) of the vertebral body. Bone velocity (BV) and broadband ultrasonic attenuation (BUA) were measured in the right calcaneus. Vertebral strength was determined by uniaxial compressive testing. Vertebral ultimate load was best correlated with DXA-determined vertebral BMD (r2 = 0.64). Of the QCT parameters, the best correlation with strength was obtained using the product of trabecular BMD and CSA (r2 = 0.61). For vertebral ultimate stress, however, the best correlation was observed with QCT-measured trabecular BMD (r2 = 0.51); the correlation with DXA-determined BMD was slightly poorer (r2 = 0.44). Calcaneal ultrasound correlated only weakly with both ultimate load and stress with correlation coefficients (r2) of 0.10-0.17, as did calcaneal BMD (r2 = 0.18). Both spinal DXA and spinal QCT were significantly (p < 0.001) better predictors of L3 ultimate load and stress than were either calcaneal ultrasound or calcaneal DXA. Multiple regression analysis revealed that calcaneal ultrasound did not significantly improve the predictive ability of either DXA or QCT for L3 ultimate load or stress. Calcaneal DXA BMD, bone velocity, and BUA correlated well with each other (r2 = 0.67-0.76), but were only modestly correlated with the DXA and QCT measurements of the vertebra. These data indicate that spinal DXA and spinal QCT provide comparable prediction of vertebral strength, but that a substantial proportion (typically 40%) of the variability in vertebral strength is unaccounted for by BMD measurements. Ultrasonic measurements at the calcaneus are poor predictors of vertebral strength in vitro, and ultrasound does not add predictive information independently of BMD. These findings contrast with emerging clinical data, suggesting that calcaneal ultrasound may be a valuable predictor of vertebral fracture risk in vivo. A possible explanation for this apparent discrepancy between in vivo and in vitro findings could be that current clinical ultrasound measurements at the calcaneus reflect factors that are related to fracture risk but not associated with bone fragility.

Absorptiometry, Photon↗

Variations in trabecular bone composition with anatomical site and age: potential implications for bone quality assessment.

Skeletal site-related differences in trabecular bone composition have been studied in autopsy samples from 63 individuals (age range 23-92 years). From each individual, bone samples were excised from the iliac crest, lumbar spine, femoral neck, and calcaneus. Samples were analyzed for their content of ash, calcium, collagen, extractable proteins, osteocalcin, and IGF-I. Significant differences were found between the skeletal sites, the lumbar spine being the least mineralized site and the femur the most. The femur and lumbar spine had a higher osteocalcin and IGF-I content compared with the other skeletal sites, suggesting a higher bone turnover rate. The intercorrelations between the anatomical sites were low for minerals and collagen but high for osteocalcin and IGF-I. The latter might indicate that the presence of these proteins in the bone matrix is mainly controlled by endocrine mechanisms which may influence the osteoblast function. Finally, regression analysis showed a significant age-related decrease of skeletal IGF-I at all sites examined. This finding supports the hypothesis of an IGF-I-mediated pathogenesis of senile osteoporosis. In summary, our data imply that a global assessment of skeletal function and bone quality, based upon analyses at one anatomical site, should be applied with caution.

Adult↗