Effect of Anorexia Nervosa on Volumetric Bone Mineral Density.

Hyperuricemia (HU) and gout are co-conditions of psoriasis and psoriatic arthritis. Current data suggest a positive association between HU and areal bone mineral density (BMD) and a negative influence of psoriasis on local bone, even in the absence of arthritis. However, the influence of the combination of HU and psoriasis on bone is still unclear. The aim of this study was to assess the impact of HU with and without psoriasis on bone microstructure and volumetric BMD (vBMD). Healthy individuals with uric acid levels within the normal range (NU), with hyperuricemia (HU), patients with hyperuricemia and psoriasis (PSO + HU), and patients with uric acid within the normal range and psoriasis (PSO + NU) were included in our study. Psoriasis patients had no current or past symptoms of arthritis. Average, trabecular, and cortical vBMD (mgHA/cm3); trabecular number (Tb.N, 1/mm) and thickness (Tb.Th, mm); inhomogeneity of the network (1/N.SD, mm); and cortical thickness (Ct.Th., mm) were carried out at the ultradistal radius using high-resolution peripheral quantitative computed tomography. In addition, bone turnover markers such as DKK-1, sclerostin, and P1NP were analyzed. In total, 130 individuals were included (44 NU participants (34% female), 50 HU (24%), 16 PSO + HU (6%), 20 PSO + NU (60%)). Subjects were aged: NU 54.5 (42.8, 62.1), HU 57.5 (18.6, 65.1), PSO + HU 52.0 (42.3, 57.8), and PSO + NU 42.5 (34.8, 56.8), respectively. After adjusting for age, sex, BMI, and diabetes, patients in the HU group revealed significantly higher values of cortical vBMD (p < 0.001) as well as cortical thickness (p = 0.04) compared to the NU group. PSO + NU showed no differences to NU, but PSO + HU demonstrated both lower average (p = 0.03) and trabecular vBMD (p = 0.02). P1NP was associated with average, cortical, and trabecular vBMD as well as cortical thickness while sclerostin levels were related to trabecular vBMD. Hyperuricemia in otherwise healthy subjects was associated with a better cortical vBMD and higher cortical thickness. However, patients with both psoriasis and hyperuricemia revealed a lower vBMD.

Introduction: Vertebral fractures (VFs) in patients with acromegaly are not associated with bone mineral density (BMD) decrease. Previous studies showed impaired trabecular bone parameters among acromegaly patients. However, recent studies suggest that cortical bone could also play a role in VF development. Objective: Evaluate the utility of dual energy x-ray absorptiometry (DXA) BMD and bone structural parameters to determine VF risk among acromegaly patients. Patients and Methods: A single-center two years prospective follow up of acromegaly patients regardless of age, gender, disease activity or associated treatments was conducted. Pituitary hormones, glucose metabolism and bone turnover markers in all subjects were assessed. Each subject had L1-4 spine, femoral neck (FN) and total hip (TH) BMD measured using DXA, and TBS measurement performed ± 7 days from blood sampling. 3D Shaper was used to assess proximal femur trabecular and cortical volumetric (v) BMD, cortical surface (s) BMD and cortical thickness (Cth). VF assessment was performed using the lateral spine imaging IVA™ mode with a Hologic Horizon® densitometer using semi-quantitative approach. Study outcomes were assessed at two time points - baseline and month 24. Results: Seventy subjects (34 M/36F), mean age 55.1 years, including 26 with active disease were studied. After two years a significant decrease in IGF-1 (-30%), osteocalcin (-18%) and TH cortical vBMD (-3%; all p≤0.05) was observed. During follow-up, 13 patients nine of them with controlled disease, developed VF; these patients had greater increase in CTx and decrease in TBS, sBMD, cortical and trabecular vBMD at TH and neck. Multivariate analysis of fracture prediction showed cortical vBMD at TH and neck as best parameters for fracture prediction with AUC 0.766 and 0.774; respectively. TBS was negatively associated with fasting plasma glucose (FPG), HBA1c at each time period. Conclusions: Decrease in cortical vBMD was the most sensitive and specific predictor of incident VF suggesting that cortical bone is involved in fracture development among acromegaly patients. In addition, TBS was strongly negatively associated with glucose metabolism, suggesting glucose intolerance could lead to trabecular bone impairment.

While anorexia nervosa is associated with impaired skeletal integrity, less is known about the skeletal effects of atypical anorexia nervosa, in which psychological criteria for anorexia nervosa are met, but affected individuals are not low weight. Mean bone mineral density (BMD) is higher in atypical anorexia nervosa than in low-weight anorexia nervosa but lower than in healthy controls. However, it is unknown whether bone microarchitecture and strength are affected. We hypothesized that bone microarchitecture and estimated strength would be impaired in women with atypical anorexia nervosa.This was a cross-sectional study of women ages 21-46 years (n=55): n=28 with atypical anorexia nervosa (body mass index (BMI) >18.5 kg/m2), n=27 healthy, normal weight, eumenorrheic controls. Exclusion criteria included use of oral contraceptives. Areal BMD (aBMD) was assessed by DXA. Volumetric BMD (vBMD), microarchitecture, and failure load (a bone strength estimate) at the distal tibia and radius were assessed by high-resolution peripheral quantitative CT.Median(IQR) BMI was lower [19.4(18.6,20.2) vs 22.2(21.5,23.0), p<0.0001] and median serum 25OH vitamin D level was higher [31(24,39) vs 22(17,25), p=0.0001] in atypical anorexia nervosa than healthy controls. In the atypical anorexia nervosa group, 89% had a history of low weight, 21% had a history of overweight/obesity, 31% had current amenorrhea, and 88% had a history of amenorrhea; median duration of anorexia nervosa was 11(5,14) years.Median lateral spine, total hip, femoral neck, and total radius aBMD Z-scores were lower in atypical anorexia nervosa than healthy controls [lateral spine: -1.1(-2.0,-0.1) vs -0.4(-0.7,0.4), total hip: -0.8(-1.3,0.2) vs 0.2(-0.4,0.7), femoral neck: -0.9(-1.4,0.1) vs -0.1(-0.9,0.6), radius: -0.2(-0.9,0.3) vs 0.1(-0.4,0.6); p≤0.04 for all]. At the tibia, median total, cortical, and trabecular vBMD; cortical thickness; trabecular bone volume fraction; and failure load were lower in atypical anorexia nervosa than healthy controls (p<0.05). At the radius, median trabecular number was lower and trabecular separation was higher in atypical anorexia nervosa than healthy controls (p≤0.04), but there was no difference in failure load between the groups. After controlling for baseline BMI, differences at the radius but not tibia remained significant. At the tibia and radius, median total vBMD, cortical vBMD, and cortical thickness were lower in atypical anorexia nervosa subjects with amenorrhea compared to healthy controls and to atypical anorexia nervosa subjects with eumenorrhea (p≤0.04).ConclusionsWe demonstrate that, despite normal weight, women with atypical anorexia nervosa have impaired vBMD, microarchitecture, and estimated strength compared to healthy controls, with differences more pronounced at the weight-bearing tibia vs non-weight-bearing radius. Individuals with amenorrhea had additional impairments in the non-weight-bearing radius, suggesting an effect of systemic estrogen deficiency. Our data suggest that current normal weight is not protective against impaired bone structure and strength in atypical anorexia nervosa.Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m.

Quantitative computed tomography (QCT) can estimate volumetric bone mineral density (vBMD) and distinguish trabecular from cortical bone. Few comprehensive studies have examined correlates of vBMD in older men. This study evaluated the impact of demographic, anthropometric, lifestyle, and medical factors on vBMD in 1172 men aged 69 to 97 years and enrolled in the Osteoporotic Fractures in Men Study (MrOS). Peripheral quantitative computed tomography (pQCT) was used to measure vBMD of the radius and tibia. The multivariable linear regression models explained up to 10% of the variance in trabecular vBMD and up to 9% of the variance in cortical vBMD. Age was not correlated with radial trabecular vBMD. Correlates associated with both cortical and trabecular vBMD were age (−), caffeine intake (−), total calcium intake (+), nontrauma fracture (−), and hypertension (+). Higher body weight was related to greater trabecular vBMD and lower cortical vBMD. Height (−), education (+), diabetes with thiazolidinedione (TZD) use (+), rheumatoid arthritis (+), using arms to stand from a chair (−), and antiandrogen use (−) were associated only with trabecular vBMD. Factors associated only with cortical vBMD included clinic site (−), androgen use (+), grip strength (+), past smoker (−), and time to complete five chair stands (−). Certain correlates of trabecular and cortical vBMD differed among older men. An ascertainment of potential risk factors associated with trabecular and cortical vBMD may lead to better understanding and preventive efforts for osteoporosis in men. © 2010 American Society for Bone and Mineral Research.

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment. © 2010 American Society for Bone and Mineral Research

Corticosteroid, Parathyroid Hormone, and Body Composition Associations With Bone Density and Structure Following Kidney Transplantation.

Spinal cord injury (SCI) induces severe losses of trabecular and cortical volumetric bone mineral density (vBMD), which cannot be discriminated with conventional dual-energy X-ray absorptiometry (DXA) analysis. The objectives were to: (i) determine the effects of SCI on areal BMD (aBMD) and vBMD determined by advanced 3D-DXA-based methods at various femoral regions and (ii) model the profiles of 3D-DXA-derived parameters with the time since injury. Eighty adult males with SCI and 25 age-matched able-bodied (AB) controls were enrolled in this study. Trabecular and cortical vBMD, cortical thickness and derived strength parameters were assessed by 3D-SHAPER® software at various femoral subregions. Individuals with SCI had significantly lower integral vBMD, trabecular vBMD, cortical vBMD, cortical thickness and derived bone strength parameters (p < 0.001 for all) in total proximal femur compared with AB controls. These alterations were approximately to the same degree for all three femoral subregions, and the difference between the two groups tended to be greater for cortical vBMD than trabecular vBMD. There were minor differences according to the lesion level (paraplegics vs tetraplegics) for all 3D-DXA-derived parameters. For total proximal femur, the decreasing bone parameters tended to reach a new steady state after 5.1years for integral vBMD, 7.4years for trabecular vBMD and 9.2years for cortical vBMD following SCI. At proximal femur, lower vBMD (integral, cortical and trabecular) and cortical thickness resulted in low estimated bone strength in individuals with SCI. It remains to be demonstrated whether these new parameters are more closely associated with fragility fracture than aBMD.

Suboptimal bone microarchitecure in adolescent girls with obesity compared to normal-weight controls and girls with anorexia nervosa.

Shorter estrogen exposure from puberty onset to peak bone mass attainment may explain how late menarche is a risk factor for osteoporosis. The influence of menarcheal age (MENA) on peak bone mass, cortical, and trabecular microstructure was studied in 124 healthy women aged 20.4 +/- 0.6 (sd) yr. At distal radius, areal bone mineral density (aBMD) was measured by dual-energy x-ray absorptiometry, and volumetric bone mineral density (BMD) and microstructure were measured by high-resolution peripheral computerized tomography, including: total, cortical, and trabecular volumetric BMD and fraction; trabecular number, thickness, and spacing; cortical thickness (CTh); and cross-sectional area (CSA). Median MENA was 12.9 yr. Mean aBMD T score of the whole cohort was slightly positive. aBMD was inversely correlated to MENA for total radius (R = -0.21; P = 0.018), diaphysis (R = -0.18; P = 0.043), and metaphysis (R = -0.19; P = 0.031). Subjects with MENA more than the median [LATER: 14.0 +/- 0.7 (+/-sd) yr] had lower aBMD than those with MENA less than the median (EARLIER: 12.1 +/- 0.7 yr) in total radius (P = 0.026), diaphysis (P = 0.042), and metaphysis (P = 0.046). LATER vs. EARLIER displayed lower total volumetric BMD (315 +/- 54 vs. 341 +/- 56 mg HA/cm(3); P = 0.010), cortical volumetric BMD (874 +/- 49 vs. 901 +/- 44 mg HA/cm(3); P = 0.003), and CTh (774 +/- 170 vs. 849 +/- 191 microm; P = 0.023). CTh was inversely related to CSA (R = -0.46; P < 0.001). In LATER reduced CTh was associated with 5% increased CSA. In healthy young adult women, a 1.9-yr difference in mean MENA was associated with lower radial aBMD T score, lower CTh without reduced CSA, a finding compatible with less endocortical accrual. It may explain how late menarche is a risk factor for forearm osteoporosis.

E-modulus mapping at bone packet level: Combination of scanning acoustic microscopy in time of flight mode and back scattered electron imaging

Forearm bone geometry and mineral content in UK women of European and South-Asian origin

Cross-sectional studies of elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density (BMD). However, as the exercise undertaken by athletes is beyond the reach of most individuals, these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community. To determine whether moderate exercise increases bone mass, size, areal, and volumetric BMD, two socioeconomically equivalent schools were randomly allocated to be the source of an exercise group or controls. Twenty boys (mean age 10.4 years, range 8.4-11.8) allocated to 8 months of 30-minute sessions of weight-bearing physical education lessons three times weekly were compared with 20 controls matched for age, standing and sitting height, weight, and baseline areal BMD. Areal BMD, measured using dual-energy X-ray absorptiometry, increased in both groups at all sites, except at the head and arms. The increase in areal BMD in the exercise group was twice that in controls; lumbar spine (0.61 +/- 0.11 vs. 0.26 +/- 0.09%/month), legs (0.76 +/- 0.07 vs. 0.34 +/- 0.08%/month), and total body (0.32 +/- 0.04 vs. 0.17 +/- 0.06%/month) (all p < 0.05). In the exercise group, femoral midshaft cortical thickness increased by 0.97 +/- 0. 32%/month due to a 0.93 +/- 0.33%/month decrease in endocortical (medullary) diameter (both p < 0.05). There was no periosteal expansion so that volumetric BMD increased by 1.14 +/- 0.33%/month, (p < 0.05). Cortical thickness and volumetric BMD did not change in controls. Femoral midshaft section modulus increased by 2.34 +/- 2. 35 cm3 in the exercise group, and 3.04 +/- 1.14 cm3 in controls (p < 0.05). The growing skeleton is sensitive to exercise. Moderate and readily accessible weight-bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness. Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition, both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause-related and age-related endocortical bone resorption.

558 Cross-sectional studies in elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density (BMD). However, as the exercise undertaken by athletes is beyond the reach of most individuals, these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community. To determine whether moderate exercise increases bone mass, size, areal and volumetric BMD, two schools were randomly allocated to an exercise or control group. Twenty boys (mean age 10.4 yrs,) allocated to 8 mths of 30 min, sessions of weight bearing physical education lessons 3 times/wk were compared with 20 controls matched for age, standing and sitting height, weight, and baseline areal BMD. Areal BMD, measured using DEXA, increased in both groups at all sites, except at the head and arms. The increase in areal BMD in the exercise group was twice that in controls; lumbar spine (0.61±0.11 vs. 0.26±0.09%/mth), legs (0.76±0.07 vs. 0.34±0.08%/mth), and total body (0.32±0.04 vs. 0.17±0.06%/mth), (all p<0.05). In the exercise group femoral midshaft cortical thickness increased by 0.97±0.32%/mth due to a 0.93±0.33%/mth decrease in endocortical (medullary) diameter (both p<0.05). There was no periosteal expansion so that volumetric BMD increased by 1.14±0.33%/mth, (p<0.05). Cortical thickness and volumetric BMD did not change in controls. Femoral midshaft section modulus increased by 2.34±2.35cm2 in the exercise group (NS), and 3.04±1.14cm2 in controls (p<0.05). Moderate and readily accessible weight bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness. Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition, both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause-related and age-related endocortical bone resorption.

Despite their higher areal bone mineral density (aBMD), adolescents with obesity (OB) have an increase in fracture risk, particularly of the extremities, compared with normal-weight controls (C). Whereas bone parameters that increase fracture risk are well characterized at the other end of nutritional spectrum in anorexia nervosa (AN), these data are lacking in adolescents with obesity. Our objective was to compare bone geometry, microarchitecture, density and strength estimates in adolescents across the nutritional spectrum, to determine whether suboptimal bone adaptation to increased body weight may explain the increased fracture risk in OB. We assessed bone endpoints in 153 adolescents 14-21 years old: 50 OB, 48 C and 55 AN. We used DXA to assess aBMD at the lumbar spine, proximal femur and whole body, high resolution peripheral quantitative CT (HRpQCT) to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and finite element analysis to assess failure load (a strength estimate) at the distal radius and tibia. All HRpQCT and FEA analyses were controlled for age. Groups did not differ for age or height. Per design, weight and BMI were highest in OB and lowest in AN. Areal BMD Z-scores at all sites were highest in OB, intermediate in C and lowest in AN (p<0.03 for all comparisons). At the radius, cortical area and thickness increased progressively from AN to C to OB (p<0.03) while trabecular area did not differ across groups. Compared to C and AN, OB had higher cortical porosity (p<0.03), trabecular number and thickness (p<0.01). Cortical vBMD did not differ in OB vs. C but was lower in AN (p<0.0001). Trabecular and total vBMD increased progressively from AN to C to OB (p<0.04). Of note, plate BV/TV did not differ in OB vs. C, but was lower in AN (p<0.0001); rod BV/TV was higher in OB vs. C and AN (p <0.002). At the tibia, cortical area and thickness increased progressively from AN to C to OB (p<0.002), while trabecular area was higher in OB vs. AN and C (p<0.004). Compared to C and AN, OB had higher cortical porosity (p<0.007) and lower trabecular thickness (p<0.02). Trabecular number increased progressively from AN to C to OB (p<0.02). Cortical vBMD did not differ in OB vs. C but was lower in AN (p<0.02). Trabecular and total vBMD were higher in OB vs. AN and C (p<0.002). Plate BV/TV was comparable in the three groups but rod BV/TV was higher in OB vs. C and AN (p<0.0001). Finally, failure load (a strength estimate) increased from AN to C to OB for the radius and tibia (p<0.04 for all). However, after adjusting for weight, failure load was lower in OB vs. C at both sites (p<0.05), and did not differ from AN. These data demonstrate that not all bone parameters appropriately adapt to an increase in body weight, with cortical porosity, cortical vBMD, and plate BV/TV at the radius and tibia, and tibial trabecular thickness being particularly at risk. These changes may explain the higher risk for fracture in OB than controls.

Bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) is areal and in the unit of g/cm2, while BMD measured by quantitative computed tomography (QCT) is volumetric and in the unit of g/cm3. There is often a need to convert them to each other, but a simple conversion method is not available. The objective of this study was to establish empirical functions for the conversion. QCT of left femur from 67 subjects were acquired from a local clinical centre. For each subject, volumetric BMD was extracted from QCT using QCT Pro; the corresponding areal BMD was measured by CTXA-Hip. Both QCT Pro and CTXA-Hip are commercial software. The paired volumetric and areal BMD datasets were randomly split into two groups, and used respectively in construction and validation of empirical functions. Correlation between volumetric and areal BMD was 0.9073 (p < 0.0001) without considering femoral neck width (FNW), and 0.9970 (p < 0.0001) with the consideration of FNW. In the validations, the best agreement between predicted and measured volumetric BMD was R2 = 0.9796, SSE = 0.0074, CV = 2.7%; the best agreement between predicted and measured areal BMD was R2 = 0.9713, SSE = 0.0072, CV = 2.8%. Femur size represented by FNW had substantial effect on correlation between areal and volumetric BMD. With the consideration of FNW, areal and volumetric BMD can be converted to each other using the empirical functions constructed in this study.