Estrogen-specific action on bone geometry and volumetric bone density: Longitudinal observations in an adult with complete androgen insensitivity

IntroductionSex steroids have distinct effects on bone growth and maintenance in men and women, mediated through their respective steroid receptors. Though most evidence is derived from animal studies, several concepts have been confirmed in humans by detection of specific mutations. In this report we describe changes in bone size and volumetric bone density in a complete androgen insensitive subject (CAIS) due to a mutation in the androgen receptor during 5 years of estrogen treatment.Materials and methodsWe present a case report of a 31 year old XY female with CAIS with a longitudinal follow-up for 5 years of areal and volumetric bone parameters. Areal and volumetric bone parameters were determined using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Sex steroids, LH, FSH and IGF-I were determined by immunoassay.ResultsComplete androgen insensitivity syndrome was genetically confirmed by detection of the mutation Asp767Tyr in the androgen receptor gene. Bone size at presentation was found to be intermediate between male and female reference values. Low areal and volumetric bone density (both trabecular and cortical) was observed at baseline and improved gradually with estrogen treatment (+ 2% to 6.5%). Upon estrogen treatment, endosteal contraction (? 1%) was demonstrated, with increasing cortical thickness (+ 3%), cortical area (+ 5%) and unchanged periosteal circumference.ConclusionsDuring adult life, estrogens mediate endosteal bone apposition and volumetric bone density, without marked influence on periosteal bone apposition. The finding of a bone size intermediate between male and female supports testosterone as an essential mediator for periosteal bone expansion, but not as the sole stimulus for bone expansion during growth.     

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.     

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.     

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.     

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.     

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.     

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.     

Structural differences in cortical shell properties between upper and lower human fibula as described by pQCT serial scans. A biomechanical interpretation

This study describes the structural features of fibula cortical shell as allowed by serial pQCT scans in 10/10 healthy men and women aged 20–40 years. Indicators of cortical mass (mineral content -BMC-, cross-sectional area -CSA-), mineralization (volumetric BMD, vBMD), design (perimeters, thickness, moments of inertia -MIs-) and strength (Bone Strength Indices, BSIs; polar Strength-Strain Index, pSSI) were determined. All cross-sectional shapes and geometrical or strength indicators suggested a sequence of five different regions along the bone, which would be successively adapted to 1. transmit loads from the articular surface to the cortical shell (near the proximal tibia-fibular joint), 2. favor lateral bending (central part of upper half), 3. resist lateral bending (mid-diaphysis), 4. favor lateral bending again (central part of the lower half), and 5. resist bending/torsion (distal end). Cortical BMC and the cortical/total CSA ratio were higher at the midshaft than at both bone ends (p < 0.001). However, all MIs, BSIs and pSSI values and the endocortical perimeter/cortical CSA ratio (indicator of the mechanostat's ability to re-distribute the available cortical mass) showed a “W-shaped” distribution along the bone, with maximums at the mid-shaft and at both bone's ends (site effect, p < 0.001). The correlation coefficient (r) of the relationship between MIs (y) and cortical vBMD (x) at each bone site (“distribution/quality” curve that describes the efficiency of distribution of the cortical tissue as a function of the local tissue stiffness) was higher at proximal than distal bone regions (p < 0.001). The results from the study suggest that human fibula is primarily adapted to resist bending and torsion rather than compression stresses, and that fibula's bending strength is lower at the center of its proximal and distal halves and higher at the mid-shaft and at both bone's ends. This would favor, proximally, the elastic absorption of energy by the attached muscles that rotate or evert the foot, and distally, the widening of the heel joint and the resistance to excessive lateral bending. Results also suggest that biomechanical control of structural stiffness differs between proximal and distal fibula.     

Distal Radius Strength: A Comparison of DXA-Derived vs pQCT-Measured Parameters in Adolescent Females

Although quantitative computed tomography (QCT) is considered the gold standard for in vivo densitometry, dual-energy X-ray absorptiometry (DXA) scans assess larger bone regions and are more appropriate for pediatric longitudinal studies. Unfortunately, DXA does not yield specific bone architectural output. To address this issue in healthy, postmenarcheal girls, Sievänen's distal radius formulae [1996] were applied to derive indices of bone geometry, volumetric bone mineral density (vBMD), and strength from DXA data; results were compared to peripheral quantitative computed tomography (pQCT) output. Contemporaneous scans were performed on the left, distal radii of 35 gymnasts, ex-gymnasts, and nongymnasts (aged 13.3–20.4 yr, mean 16.6 yr). For 4% and 33% regions, pQCT measured cross-sectional areas (CSAs) and vBMD; comparable DXA indices were generated at ultradistal and 1/3 regions. Index of structural strength in axial compression was calculated from 4% pQCT and DXA output for comparison; 33% pQCT strength-strain index was compared to 1/3 DXA section modulus. Sievänen DXA indices were significantly, positively correlated with pQCT output (R = +0.61 to +0.98; p < 0.0001). At the distal radius, in healthy postmenarcheal girls, Sievänen's method yielded potentially useful DXA indices of diaphyseal cortical CSA and bone strength at both the diaphysis (section modulus) and the metaphysis (index of structural strength in axial compression).     

Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content (BMC) and density (BMD) and determined the contribution of inflammatory markers to 1-yr changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss project who were randomly assigned to 1 of 3 treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy X-ray absorptiometry and the 4% distal tibia by peripheral quantitative computed tomography. Serum inflammatory markers (C-reactive protein, interleukin [IL]-1β, IL-6, tumor necrosis factor-alpha [TNF-α], and white blood cell count [WBC]) were measured at baseline, 6, and 12 mo. Because of attrition or missing values, data analysis at 12 mo includes only 235 women. Significant associations among IL-6, TNF-α, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1–6.1% of the variance to the observed 12-mo changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss.     

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.     

Longitudinal Change in Bone Density,Geometry, and Estimated Bone Strength in Older Men and Women From The Gambia: Findings From the Gambian Bone and Muscle Aging Study (GamBAS)

Musculoskeletal aging in the most resource-limited countries has not been quantified, and longitudinal data are urgently needed to inform policy. The aim of this prospective study was to describe musculoskeletal aging in Gambian adults. A total of 488 participants were recruited stratified by sex and 5-year age band (aged 40 years and older); 386 attended follow-up 1.7 years later. Outcomes were dual-energy X-ray absorptiometry (DXA) (n = 383) total hip areal bone mineral density (aBMD), bone mineral content (BMC), bone area (BA); peripheral quantitative computed tomography (pQCT) diaphyseal and epiphyseal radius and tibia (n = 313) total volumetric BMD (vBMD), trabecular vBMD, estimated bone strength indices (BSIc), cross-sectional area (CSA), BMC, and cortical vBMD. Mean annualized percentage change in bone outcomes was assessed in 10-year age bands and linear trends for age assessed. Bone turnover markers, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were explored as predictors of change in bone. Bone loss was observed at all sites, with an annual loss of total hip aBMD of 1.2% in women after age 50 years and in men at age 70 years plus. Greater loss in vBMD and BSIc was found at the radius in both men and women; strength was reduced by 4% per year in women and 3% per year in men (p trend 0.02, 0.03, respectively). At cortical sites, reductions in BMC, CSA, and vBMD were observed, being greatest in BMC in women, between 1.4% and 2.0% per annum. Higher CTX and PINP predicted greater loss of trabecular vBMD in women and BMC in men at the radius, and higher 25(OH)D with less loss of tibial trabecular vBMD and CSA in women. The magnitude of bone loss was like those reported in countries where fragility fracture rates are much higher. Given the predicted rise in fracture rates in resource-poor countries such as The Gambia, these data provide important insights into musculoskeletal health in this population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Effects of sciatic neurectomy on the femur in growing rats: Application of peripheral quantitative computed tomography and Fourier transform infrared spectroscopy

The effects of unilateral sciatic neurectomy (USN) on the development of the femur were studied in 15 growing Wistar-derived rats (age, 5 weeks). The rats were divided into four groups: USN-operated group (right femur), USN-nonoperated group (left femur), sham-operated group (right femur), and sham-nonoperated group (left femur). Bone mineral density (BMD), bone mineral content (BMC), bone area, periosteal circumference, and endosteal circumference were measured by peripheral quantitative computed tomography (pQCT) and the mineral/matrix ratio was evaluated by Fourier transform infrared spectroscopy (FTIR). The USN-operated group showed a significant decrease in cortical BMC, bone area, and periosteal circumference compared with the other groups (P < 0.05). The cortical BMD did not vary significantly between the groups. In the cancellous bone, the USN-operated group showed a significant decrease in BMD and BMC at the metaphysis compared with the other groups (P < 0.05). The mineral/matrix ratio of the cortical bone did not differ significantly between the USN-operated and USN-nonoperated groups. These results suggest that in cortical bone, USN inhibits periosteal bone formation but has no significant effect on the mineral/matrix ratio of cortical bone in femurs. In cancellous bone, USN induces bone loss at the metaphysis. Received: Nov. 19, 1998 / Accepted: Feb. 12, 1999     

Reference Data for Bone Mineral Density in Swedish Women Using Digital X-Ray Radiometry

During the last decade, digital X-ray radiometry (DXR) has been used to measure bone mineral density (BMD) in the metacarpal bones. The aim of this study was to establish Swedish reference material for bone mass in women, measured in the metacarpal bones with DXR, and compare these data with the data from the manufacturer. A sample of 1440 women aged 20–79 yr living in Örebro County was randomly assigned from the population register. Microdose mammography was used (Sectra MDM L30; Sectra Imtec AB, Linköping, Sweden) to measure BMD. Cole's LMS method was used to calculate DXR. Six hundred sixty-nine (48.3%) women participated. Peak bone mass occurred at the age of 43.4 yr with a BMD of 0.597 g/cm² (standard deviation: 0.050). Our Swedish data correlated well with the manufacturer's material. Only among women aged 50–59 yr did BMD differ, where the Swedish sample had lower values. The LMS method can be used to describe the DXR data and provide a more detailed picture of bone density distribution. DXR-BMD in Swedish women aged 20–79 yr is equivalent to findings from other studies, showing the same distribution of BMD in most age groups except for ages 50–59 yr.     

Accuracy and precision of peripheral quantitative computed tomography measurements at the tibial metaphysis.

The ability of 29 peripheral quantitative computed tomography (pQCT) software analysis modes at defining cortical from trabecular bone at three tibial metaphyseal regions was evaluated using five cadaveric tibiae. The accuracy of pQCT was determined by comparing the bone mineral content (BMC) with the ash weight. The precision of the pQCT scanner was calculated using repeated measurements. All the analysis modes had a good accuracy when measuring total bone area and a poor accuracy when measuring cortical bone area at the proximal 5% and distal 4% regions. For trabecular bone measured at all three regions and cortical bone area measured at the proximal 10% region, the Stratec peel mode 5 was the most accurate analysis mode. Highly significant correlations (r = 0.71-0.98) and a moderate accuracy error (coefficient of variation [CV] = 5-22%) was found between ash weight and BMC when using this mode. The precision of bone mineral density (BMD) measurements was good (total, CV = 2-5%; trabecular, CV = 2-5%; cortical, CV = 4-6%). pQCT is a moderately accurate, precise method of measuring trabecular and total BMD at the tibial metaphysis. The authors recommend caution when interpreting results for cortical BMD, as cortical area measurements at the metaphyseal region are less accurate and less precise.     

Adiponectin and its association with bone mass accrual in childhood

Circulating adiponectin levels are inversely related to bone mineral density (BMD) in humans and animal models. Previous studies in humans have been confined largely to adult populations, and whether adiponectin influences bone mass accrual in childhood is unclear. We examined this question using the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort by investigating relationships between circulating adiponectin levels at a mean age of 9.9 years, indices of bone mass as measured by total‐body dual‐energy X‐ray absorptiometry (DXA) at ages 9.9 and 15.5 years, and cortical bone parameters as measured by peripheral quantitative computed tomography (pQCT) of the midtibia at age 15.5 years. A total of 4927 children were included at age 9.9 years, of whom 97% and 90% of boys and girls, respectively, were in prepuberty or early puberty, as defined by Tanner stage 1–2. A total of 2754 children were included at age 15.5 years, of whom 95% and 97% of boys and girls, respectively, were in late puberty, as defined by Tanner stage 4–5. Circulating adiponectin was found to be related to fat mass, lean mass, and, to a lesser extent, height, so analyses were adjusted for these three variables to identify possible independent effects of adiponectin on bone development. Adiponectin was inversely related to total‐body‐less‐head bone mineral content (BMC; ?3.0%), bone area (BA; ?1.8%), BMC divided by BA (BMD; ?4.8%), and BMC adjusted for BA by linear regression (aBMC; ?5.6%), as measured at age 9.9 years (coefficients show change per doubling in adiponectin concentration, p < .001). Consistent with these results, inverse associations also were seen between adiponectin and cortical BMC (?4.8%) and cortical bone area (?4.7%), as measured by tibial pQCT at age 15.5 years (p < .001). Further pQCT results suggested that this inverse association of adiponectin with skeletal development predominantly involved a negative association with endosteal relative to periosteal expansion, as reflected by cortical thickness (?6.0%, p < .001). We conclude that, independent of fat mass, lean mass, and height, adiponectin is associated with lower bone mass in childhood predominantly owing to an influence on relative endosteal expansion. Since these associations were observed before and after puberty, this suggests that setting of adiponectin levels in midchildhood has the potential to exert long‐term effects on bone strength and fracture risk. © 2010 American Society for Bone and Mineral Research.     

Regular exercise limits alcohol effects on trabecular,cortical thickness and porosity,and osteocyte apoptosis in the rat

IntroductionExcessive alcohol consumption is known to be a cause of secondary osteoporosis whereas physical activity is recommended in prevention of osteoporosis. This study was designed to analyze the effects of physical exercise on bone parameters in chronic alcohol-fed rats.MethodsForty-eight male Wistar rats were divided in four groups: Control (C), Alcohol (A), Exercise (E) and Alcohol + Exercise (AE). A and AE groups drank a solution composed of ethanol and water (35% volume/volume for 17 weeks). E and AE groups were submitted to treadmill training for 14 weeks (60 min/day, 5 times/week). Bone mineral density (BMD) was assessed by DXA, the trabecular and cortical microarchitectural parameters by microCT and serum osteocalcin, NTx and leptin concentrations by ELISA assays. Bone mechanical parameters were evaluated through mechanical testing. Osteocyte apoptosis was analyzed with cleaved caspase-3 immunostaining.ResultsAlcohol-fed rats had significantly lower body weight (?28%), fat (?46%) and lean mass (?25%) compared to controls. BMD (?8%), trabecular (?12%) and cortical thickness (?27%) were significantly lower with alcohol whereas porosity (+38%) and pore number (+42%) were higher. Exercise combined with alcohol prevented lower Tb.Th (+20%), Ct.Th (+30%), stress (+26%) and higher Ct.Po (?24%) and osteocyte apoptosis (?91%) compared to A. However, WB BMD (?4%) and femur BMD were still lower in AE versus C.ConclusionRegular physical activity has beneficial effects on some microarchitectural parameters in alcohol-fed rats. However, regular treadmill exercise does not compensate for the effects of heavy chronic alcohol consumption on whole body bone density.     

Current and past menstrual status is an important determinant of femoral neck geometry in exercising women

Menstrual status, both past and current, has been established as an important determinant of bone mineral density (BMD) in young exercising women. However, little is known regarding the association between the cumulative effect of menstrual status and indices of bone health beyond BMD, such as bone geometry and estimated bone strength.PurposeThis study explores the association between cumulative menstrual status and indices of bone health assessed using dual-energy x-ray absorptiometry (DXA), including femoral neck geometry and strength and areal BMD (aBMD), in exercising women.Methods101 exercising women (22.0 ± 0.4 years, BMI 21.0 ± 0.2 kg/m², 520 ± 40 min/week of self-reported exercise) participated in this cross-sectional study. Women were divided into three groups as follows based on their self-reported current and past menstrual status: 1) current and past regular menstrual cycles (C + P-R) (n = 23), 2) current and past irregular menstrual cycles (C + P-IR) (n = 56), 3) and current or past irregular cycles (C/P-RIR) (n = 22). Current menstrual status was confirmed using daily urinary metabolites of reproductive hormones. DXA was used to assess estimates of femoral neck geometry and strength from hip strength analysis (HSA), aBMD, and body composition. Cross-sectional moment of inertia (CSMI), cross-sectional area (CSA), strength index (SI), diameter, and section modulus (Z) were calculated at the femoral neck. Low CSMI, CSA, SI, diameter, and Z were operationally defined as values below the median. Areal BMD (g/cm²) and Z-scores were determined at the lumbar spine, femoral neck, and total hip. Low BMD was defined as a Z-score < − 1.0. Chi-square tests and multivariable logistic regression were performed to compare the prevalence and determine the odds, respectively, of low bone geometry, strength, and aBMD among groups.ResultsCumulative menstrual status was identified as a significant predictor of low femoral neck CSMI (p = 0.005), CSA (p ≤ 0.024), and diameter (p = 0.042) after controlling for confounding variables. C + P-IR or C/P-RIR were four to eight times more likely to exhibit low femoral neck CSMI or CSA when compared with C + P-R. Lumbar spine aBMD and Z-score were lower in C + P-IR when compared with C + P-R (p ≤ 0.003). A significant association between menstrual group and low aBMD was observed at the lumbar spine (p = 0.006) but not at the femoral neck or total hip (p > 0.05). However, after controlling for confounding variables, cumulative menstrual status was not a significant predictor of low aBMD.ConclusionIn exercising women, the cumulative effect of current and past menstrual irregularity appears to be an important predictor of lower estimates of femoral neck geometry, as observed by smaller CSMI and CSA, which may serve as an another means, beyond BMD, by which menstrual irregularity compromises bone strength. As such, evaluation of both current and past menstrual status is recommended to determine potential risk for relatively small bone geometry at the femoral neck.     

Bone turnover markers are associated with higher cortical porosity,thinner cortices,and larger size of the proximal femur and non-vertebral fractures

Bone turnover markers (BTM) predict bone loss and fragility fracture. Although cortical porosity and cortical thinning are important determinants of bone strength, the relationship between BTM and cortical porosity has, however, remained elusive. We therefore wanted to examine the relationship of BTM with cortical porosity and risk of non-vertebral fracture.In 211 postmenopausal women aged 54–94 years with non-vertebral fractures and 232 age-matched fracture-free controls from the Tromsø Study, Norway, we quantified femoral neck areal bone mineral density (FN aBMD), femoral subtrochanteric bone architecture, and assessed serum levels of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX).Fracture cases exhibited higher PINP and CTX levels, lower FN aBMD, larger total and medullary cross-sectional area (CSA), thinner cortices, and higher cortical porosity of the femoral subtrochanter than controls (p ≤ 0.01). Each SD increment in PINP and CTX was associated with 0.21–0.26 SD lower total volumetric BMD, 0.10–0.14 SD larger total CSA, 0.14–0.18 SD larger medullary CSA, 0.13–0.18 SD thinner cortices, and 0.27–0.33 SD higher porosity of the total cortex, compact cortex, and transitional zone (all p ≤ 0.01). Moreover, each SD of higher PINP and CTX was associated with increased odds for fracture after adjustment for age, height, and weight (ORs 1.49; 95% CI, 1.20–1.85 and OR 1.22; 95% CI, 1.00–1.49, both p < 0.05). PINP, but not CTX, remained associated with fracture after accounting for FN aBMD, cortical porosity or cortical thickness (OR ranging from 1.31 to 1.39, p ranging from 0.005 to 0.028).In summary, increased BTM levels are associated with higher cortical porosity, thinner cortices, larger bone size and higher odds for fracture. We infer that this is produced by increased periosteal apposition, intracortical and endocortical remodeling; and that these changes in bone architecture are predisposing to fracture.