Background

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.

Methods

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+).

Results

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.

Conclusions

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.

Purpose

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.

Results

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.

Conclusion

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.

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.

Trial Registration

ClinicalTrials.gov NCT00690417

Trial Registration

ClinicalTrials.gov NCT01049048

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.

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Introduction

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.

Methods

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.

Results

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.

Conclusions

Optimal glycemic control may prevent low BMD and altered bone turnover in type 1 diabetes, and decrease fracture risk.

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.

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.