Osteoporosis is a prevalent but underdiagnosed condition.
To evaluate computed tomography (CT)-derived bone mineral density (BMD) assessment compared with dual-energy x-ray absorptiometry (DXA) measures for identifying osteoporosis by using CT scans performed for other clinical indications.
Single academic health center.
1867 adults undergoing CT and DXA (n = 2067 pairs) within a 6-month period over 10 years.
CT-attenuation values (in Hounsfield units [HU]) of trabecular bone between the T12 and L5 vertebral levels, with an emphasis on L1 measures (study test); DXA BMD measures (reference standard). Sagittal CT images assessed for moderate-to-severe vertebral fractures.
CT-attenuation values were significantly lower at all vertebral levels for patients with DXA-defined osteoporosis (P < 0.001). An L1 CT-attenuation threshold of 160 HU or less was 90% sensitive and a threshold of 110 HU was more than 90% specific for distinguishing osteoporosis from osteopenia and normal BMD. Positive predictive values for osteoporosis were 68% or greater at L1 CT-attenuation thresholds less than 100 HU; negative predictive values were 99% at thresholds greater than 200 HU. Among 119 patients with at least 1 moderate-to-severe vertebral fracture, 62 (52.1%) had nonosteoporotic T-scores (DXA false-negative results), and most (97%) had L1 or mean T12 to L5 vertebral attenuation of 145 HU or less. Similar performance was seen at all vertebral levels. Intravenous contrast did not affect CT performance.
The potential benefits and costs of using the various CT-attenuation thresholds identified were not formally assessed.
Abdominal CT images obtained for other reasons that include the lumbar spine can be used to identify patients with osteoporosis or normal BMD without additional radiation exposure or cost.
Primary Funding Source
National Institutes of Health.
Adult bone mass depends on acquisition in childhood and decline in adulthood, and may be influenced by socioeconomic conditions over the entire life course.
We examined associations of bone mineral density (BMD) in adulthood with life course socioeconomic status in 729 participants in the Midlife in the United States Biomarker Project, adjusting for age, menopausal transition stage, race, gender, body weight, smoking, physical activity in several life stages, and research site. Primary predictors were a) childhood socioeconomic advantage score (including parental education, self-rated financial status relative to others, not being on welfare), b) adult education level (no college vs. some college vs. college graduate), and c) adult current financial advantage score (including family-adjusted poverty to income ratio, self-assessed current financial situation, having enough money to meet needs, ease in paying bills).
Mean age was 56.9 (range 34–85) years. After adjustment for covariates, childhood socioeconomic advantage and adult education level were positively associated with lumbar spine BMD: 0.27 standard deviations (SD) higher at 90th compared to 10th percentile of childhood advantage score (P = 0.009), and 0.24 SD higher in college graduates compared to participants without college education (P = 0.01). Adult current financial advantage was not associated with lumbar spine BMD. None of the three socioeconomic indicators was significantly associated with femoral neck BMD.
Childhood socioeconomic advantage and adult education level were associated with higher adult lumbar spine BMD. Current financial advantage was not associated with BMD. Childhood socioeconomic factors may influence acquisition of lumbar BMD.
bone mineral density; socioeconomic status; poverty; education; income
To compare microscopic magnetic resonance imaging (μMRI) parameters of trabecular micro-architecture between postmenopausal women with and without fracture who have normal or osteopenic bone mineral density (BMD) on dual-energy x-ray absorptiometry (DXA).
The study included 36 post-menopausal Caucasian women 50 years of age and older with normal or osteopenic BMD (T-scores better than −2.5 at the lumbar spine, proximal femur, and one-third radius on DXA). Eighteen women had a history of low-energy fracture, while 18 women had no history of fracture and served as an age, race, and ultra-distal radius BMD-matched control group. A three-dimensional fast large-angle spin-echo (FLASE) sequence with 137 μm × 137 μm × 400 μm resolution was performed through the non-dominant wrist of all 36 women using the same 1.5T scanner. The high resolution images were used to measure trabecular bone volume fraction, trabecular thickness, surface-to-curve ratio, and erosion index. Wilcoxon signed rank tests were used to compare differences in BMD and μMRI parameters between post-menopausal women with and without fracture.
Post-menopausal women with fracture had significantly lower (p<0.05) trabecular bone volume fraction and surface-to-curve ratio and significantly higher (p<0.05) erosion index than post-menopausal women without fracture. There was no significant difference between post-menopausal women with and without fracture in trabecular thickness (p=0.80) and BMD of the spine (p=0.21), proximal femur (p=0.19), one-third radius (p=0.47), and ultra-distal radius (p=0.90).
Post-menopausal women with normal or osteopenic BMD who had a history of low energy fracture had significantly different (p<0.05) μMRI parameters than an age, race, and ultra-distal radius BMD-matched control group of postmenopausal women with no history of fracture. Our study suggests that μMRI can be used to identify individuals without a DXA-based diagnosis of osteoporosis who have impaired trabecular micro-architecture and thus a heretofore-unappreciated elevated fracture risk.
Osteoporosis; Trabecular Micro-Architecture; Magnetic Resonance Imaging; Fracture
To determine socioeconomic status (SES) and race differences in levels of bone turnover.
Using data from the Biomarker Substudy of the Midlife in the U.S. (MIDUS) study (491 men, 449 women), we examined cross-sectional associations of SES and race with serum levels of bone turnover markers (bone-specific alkaline phosphatase [BSAP], procollagen type I N-terminal propeptide [PINP], and N-telopeptide [Ntx]) separately in men and women. Linear multivariable regression was used to control for body weight, menopausal transition stage, and age.
Among men, low family poverty-to-income ratio (FPIR) was associated with higher turnover, but neither education nor race was associated with turnover. Men with FPIR <3 had 1.808 nM BCE higher Ntx (P = 0.05), 3.366 U/L higher BSAP (P = 0.02), and 7.066 higher PINP (P = 0.02). Among women, neither education nor FPIR was associated with bone turnover, but Black women had 3.688 nM BCE higher Ntx (P = 0.001), 5.267 U/L higher BSAP (P=0.005), and 11.906 μg/L higher PINP (P=0.008) compared to non-Black women.
Economic adversity was associated with higher bone turnover in men, and minority race status was associated with higher bone turnover in women, consistent with the hypothesis that higher levels of social stresses cause increased bone turnover. The magnitude of these associations was comparable to the effects of some osteoporosis medications on levels of turnover.
bone turnover; bone resorption; socioeconomic status; SES; N-telopeptide; bone-specific alkaline phosphatase; procollagen type I N-terminal propeptide; poverty; income; Ntx; PINP; BSAP
A clinical need exists to improve identification of those who will sustain fragility fractures. Individuals with both osteoporosis (OP) and sarcopenia (SP), so-called “sarco-osteoporosis” (SOP), might be at higher fracture risk than those with OP or SP alone. Approaches to facilitate SOP identification, e.g., use of tallest historical rather than current height and inclusion of radius bone mineral density (BMD) measurement, may be of benefit. This study examined the effect of advancing age on SOP prevalence with and without use of historical tallest height and radius BMD measurement.
Adults age 60+ underwent dual-energy X-ray absorptiometry (DXA) BMD and total body composition measurement. OP and SP were defined using standard criteria: T-score ≤−2.5 at the lumbar spine or hip and appendicular lean mass (ALM)/current height2 <5.45 kg/m2 (female) and <7.26 kg/m2 (male). Proposed “sensitive” SP criteria used historical tallest height instead of current height, while “sensitive” OP criteria added the 1/3rd radius T-score. The primary outcome was SOP prevalence by decade (60–69, 70–79, 80+).
A total of 304 individuals (146 M/158 F) participated. OP, SP and SOP prevalence were higher in older adults and increased (p < 0.05) with the “sensitive” criteria. SOP prevalence was lower than that of OP or SP and increased (standard/sensitive) criteria from 1.1 % / 4.5 % in the 60–69 years age group to 10.4 % / 21.9 % in the 80+ years age group.
SOP prevalence is higher in older adults. Use of historical tallest height and 1/3rd radius BMD increases SOP prevalence. Future studies need to assess whether having SOP increases fracture risk and whether use of tallest height and/or one-third radius BMD improves fracture risk prediction.
Sarcopenia; Osteoporosis; Age; Radius BMD; Sarco-osteoporosis
To evaluate the utility of lumbar spine attenuation measurement for bone mineral density (BMD) assessment at screening CT colonography (CTC), using central dual-energy x-ray absorptiometry (DXA) as the reference standard.
Material and Methods
252 adults (240 women, 12 men; mean age, 58.9 years) underwent CTC screening and central DXA BMD measurement within 2 months (mean interval, 25.0 days). The lowest DXA T-score between the spine and hip served as the reference standard, with low BMD defined per WHO as osteoporosis (DXA T-score ≤-2.5) or osteopenia (DXA T-score between −1.0 and −2.4). Both phantomless QCT and simple non-angled ROI MDCT attenuation measurements were applied to T12-L5 levels. Ability to predict osteoporosis and low BMD (osteoporosis or osteopenia) by DXA was assessed.
A BMD cut-off of 90 mg/cc at phantomless QCT yielded 100% sensitivity for osteoporosis (29/29) and specificity of 63.8% (143/224); 87.2% (96/110) below this threshold had low BMD and 49.6% (69/139) above this threshold had normal BMD at DXA. At L1, a trabecular ROI attenuation cut-off of 160 HU was 100% sensitive for osteoporosis (29/29), with a specificity of 46.4% (104/224); 83.9% (125/149) below this threshold had low BMD and 57.5% (59/103) above had normal BMD at DXA. ROI performance was similar at all individual T12-L5 levels. At ROC analysis, AUC for osteoporosis was 0.888 for phantomless QCT (95% CI: 0.780–0.946) and ranged from 0.825–0.853 using trabecular ROIs at single lumbar levels (0.864 [0.752–0.930] at multivariate analysis). Supine-prone reproducibility was better with simple ROI method compared with QCT.
Both phantomless QCT and simple ROI attenuation measurements of the lumbar spine are effective for BMD screening at CTC, with high sensitivity for osteoporosis as defined by the DXA T-score.
Osteoporosis; Screening; Bone mineral density; Computed tomography; CT colonography
Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. −0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26).In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk.
This study assessed bone mineral density (BMD) comparability and precision using Lunar Prodigy and iDXA densitometers (GE Healthcare, Madison, WI) in adults. Additionally, the utility of supine forearm measurement with iDXA was investigated.
Lumbar spine and bilateral proximal femur measurements were obtained in routine clinical manner in 345 volunteers, 202 women and 143 men of mean age 52.5 (range: 20.1–91.6) yr. Seated and supine distal forearm scans were obtained in a subset (n = 50). Lumbar spine and proximal femur precision assessments were performed on each instrument following International Society for Clinical Densitometry recommendations in 30 postmenopausal women.
BMD at the L1–L4 spine, total proximal femur, and femoral neck was very highly correlated (r2 ≥ 0.98) between densitometers, as was the one-third radius site (r2 5 0.96). Bland-Altman analyses demonstrated no clinically significant bias at all evaluated sites. BMD precision was similar between instruments at the L1–L4 spine, mean total proximal femur, and femoral neck. Finally, one-third radius BMD measurements in the supine vs seated position on the iDXA were highly correlated (r2 = 0.96). In conclusion, there is excellent BMD correlation between iDXA and Prodigy densitometers. Similarly, BMD precision is comparable with these two instruments.
Bone densitometry; iDXA; osteoporosis; precision; prodigy
Historically, methodological differences and lack of standardization led to between-laboratory variability in 25(OH)D results. Recent observations raised concern about persisting variability. This quality assurance exercise investigated 25(OH)D result comparability between laboratories.
Serum pools (n = 25) were prepared to contain endogenous 25(OH)D2 and 25(OH)D3 at 25(OH)D concentrations from ∼12-150 nmol/L (5-60 ng/mL). Aliquots were sent to 8 laboratories utilizing various 25(OH)D assay methods including high performance liquid chromatography with ultraviolet detection (LC-UV), LC with tandem mass spectroscopy detection (LC-MS/MS) or an automated immunoassay (Diasorin Liaison). The LC-UV results were selected as a referent to which all others were compared using linear regression and Bland-Altman analysis.
Good correlation (R2 = 0.87 to 0.97) was observed for all laboratories. Modest systematic bias was observed for some laboratories ranging from a positive mean bias of 10.5 nmol/L (4.2 ng/mL) to a negative mean bias of 3.5 nmol/L (1.4 ng/mL). For the laboratory with the greatest bias, 22/25 results were numerically higher (mean +15.7%) than LC-UV results. For Liaison, the primary error was likely random, whereas the major LC-MS/MS assay error source were biases likely due to calibration issues.
Modest inter-laboratory variability persists in serum 25(OH)D measurement. The National Institute of Standards & Technology 25(OH)D Standard Reference and calibration materials will further improve between-laboratory agreement for chromatography-based assays.
Vitamin D; 25-hydroxyvitamin D; measurement; ergocalciferol; cholecalciferol
Low BMD and fracture may be complications of type 1 diabetes. We sought to determine the roles of bone turnover and glycemic control in the etiology of low BMD.
Premenopausal women from the Wisconsin Diabetes Registry Study and matched controls were compared (n=75 pairs). Heel and forearm BMD were measured, and hip and spine BMD were measured in a subset. Markers of bone formation (osteocalcin) and resorption (NTx), and glycemic control (HbA1c) were determined.
Age ranged from 18–50 years with a mean of 28, and 97% were Non-Hispanic white. Among women with diabetes, mean disease duration was 16 years and current HbA1c was 8%. Compared to controls, women with diabetes had a high prevalence of previous fracture (37% vs. 24%) and low BMD for age (heel or forearm: 49% vs. 31%), low heel and forearm BMD, and low osteocalcin levels. Levels of NTx were similar, suggesting uncoupled turnover favoring resorption. Poor glycemic control was associated with low BMD at all bone sites except the spine, and with low osteocalcin and NTx levels.
Optimal glycemic control may prevent low BMD and altered bone turnover in type 1 diabetes, and decrease fracture risk.
bone mineral density; bone turnover; diabetes mellitus, type 1; glycemic control; premenopausal
Antioxidant defenses may be compromised in osteoporotic women. Little is known about fruit and vegetable or carotenoid consumption among postmenopausal women. The primary carotenoids in human serum are α- and β-carotene, lycopene, β-cryptoxanthin, lutein, and zeaxanthin. This study investigated the interrelationships among serum carotenoid concentrations, fruit and vegetable intake, and osteoporosis in postmenopausal women (n = 59, 62.7 ± 8.8 y). Bone density was assessed by dual energy x-ray absorptiometry and osteoporosis diagnosis was based upon T-scores. Serum samples (n = 53) and 3-day diet records (n = 49) were analyzed. Logistic regression analyzed differences between carotenoids after adjusting for serum retinol; supplement usage; milk, yogurt, fruit, and vegetable intake; and BMI. Pearson statistics correlated carotenoids with specific fruit or vegetable intake. Serum lycopene concentrations were lower in the osteoporosis group than controls (p = 0.03). β-Cryptoxanthin intake was higher in the osteoporosis group (p = 0.0046). Total fruit and vegetable intakes were correlated with serum lycopene and β-cryptoxanthin (p = 0.03, 0.006, respectively). Serum α-carotene concentration was associated with carrot intake, and zeaxanthin and β-cryptoxanthin with lettuce intake. Carotenoids that may have beneficial skeletal effects are lower in women with osteoporosis. Research is needed to identify potential protective mechanisms or utilization of carotenoids during osteoporosis.
β-cryptoxanthin; carotenoids; lycopene; osteoporosis; postmenopausal women
Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D3 and its metabolic product—25(OH)D3 has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6,400 IU vitamin D3/day for six months.
Results: 1) The relationship between circulating vitamin D3 and 25(OH)D in both groups was not linear, but appeared saturable and controlled; 2) Optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D3 and 25(OH)D exceeded 0.3; at this point, the Vmax of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol.
We hypothesize that as humans live today, the 25-hydroxylase operates well below its Vmax because of chronic substrate deficiency, namely vitamin D3. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be.
vitamin D; 25-hydroxyvitamin D; nutritional vitamin D status