Clinical utility of bone turnover markers in patients with chronic kidney disease.

PURPOSE OF REVIEW: The burden of fractures is very high in patients with chronic kidney disease (CKD). It is increasingly recognized that knowledge of bone turnover is of paramount importance in guiding mineral metabolism and osteoporosis therapy in CKD. Bone histomorphometry is the gold standard to assess bone turnover, but is seldomly performed in clinical practice. Bone turnover markers (BTMs) may be the long awaited noninvasive diagnostic that may help to close the therapeutic gap in patients with advanced CKD presenting with bone fragility. RECENT FINDINGS: Mounting evidence indicates that BTMs may be useful in skeletal and nonskeletal risk stratification, in guiding mineral metabolism and osteoporosis therapy, and in monitoring the therapeutic response. SUMMARY: BTMs provide information that is complementary to other clinical tests. It may be envisioned that in the near future, the assessment of nonkidney cleared BTMs may become part of routine clinical evaluation and monitoring of bone health in CKD patients, integrated with clinical risk factors, imaging data and, eventually, bone histomorphometry. Panels of BTMs will likely be more informative than single markers, and the same might hold true for trends as opposed to single time point data.

Sex Differences in the Association Between Bone Mineral Density and Coronary Artery Disease in Patients Referred for Cardiac Computed Tomography.

Atherosclerosis and osteoporosis are both common and preventable diseases. Evidence supports a link between coronary artery disease (CAD) and low bone mineral density (BMD). This study aimed to assess the association between thoracic spine BMD and CAD in men and women with symptoms suggestive of CAD. This cross-sectional study included 1487 (mean age 57 years (range 40-80), 47% men) patients referred for cardiac computed tomography (CT). Agatston coronary artery calcium score (CACS), CAD severity (no, mild, moderate, and severe), vessel involvement (no, 1-, 2-, and 3/left main disease), and invasive measurements were evaluated. BMD of three thoracic vertebrae was measured using quantitative CT. We used the American college of radiology cut-off values for lumbar spine BMD to categorize patients into very low (<80 mg/cm3), low (80-120 mg/cm3), or normal BMD (>120 mg/cm3). BMD as a continuous variable was included in the linear regression analyses to assess associations between CACS (CACS=0, CACS 1- 399, and CACS ≥ 400) and BMD, and CAD severity and BMD. Significant lower BMD was present with increasing CACS and stenosis degree unadjusted. Multivariate linear regression analyses in women revealed a significant correlation between BMD and CACS groups (ß = -4.06, p<0.05), but no correlation between BMD and CAD severity (ß = -1.59, p = 0.14). No association was found between BMD and CACS (ß = -1.50, p = 0.36) and CAD severity (ß = 0.07, p = 0.94) in men. BMD is significantly correlated to CACS after adjusting for confounders in women, but not in men, suggesting a possible sex difference in pathophysiology.

Thoracic Bone Mineral Density Derived from Cardiac CT Is Associated with Greater Fracture Rate.

Background Osteoporosis is a prevalent, under-diagnosed, and treatable disease associated with increased fracture risk. Bone mineral density (BMD) derived from cardiac CT may be used to determine fracture rate. Purpose To assess the association between fracture rate and thoracic BMD derived from cardiac CT. Materials and Methods This prospective cohort study included consecutive participants referred for cardiac CT for evaluation of ischemic heart disease between September 2014 and March 2016. End of follow-up was June 30, 2018. In all participants, volumetric BMD of three thoracic vertebrae was measured by using quantitative CT software. The primary and secondary outcomes were any incident fracture and any incident osteoporosis-related fracture registered in the National Patient Registry, respectively. Hazard ratios were assessed by using BMD categorized as very low (<80 mg/cm3), low (80-120 mg/cm3), or normal (>120 mg/cm3). The study is registered at ClinicalTrials.gov (identifier: NCT02264717). Results In total, 1487 participants (mean age, 57 years ± 9; age range, 40-80 years; 52.5% women) were included, of whom 179 (12.0%) had very low BMD. During follow-up (median follow-up, 3.1 years; interquartile range, 2.7-3.4 years; range, 0.2-3.8 years), 80 of 1487 (5.3%) participants were diagnosed with an incident fracture and in 31 of 80 participants, the fracture was osteoporosis related. In unadjusted Cox regressions analyses, very low BMD was association with a greater rate of any fracture (hazard ratio, 2.6; 95% confidence interval [CI]: 1.4, 4.7; P = .002) and any osteoporosis-related fracture (hazard ratio, 8.1; 95% CI: 2.4, 26.7; P = .001) compared with normal BMD. After adjusting for age and sex, very low BMD remained associated with any fracture (hazard ratio, 2.1; 95% CI: 1.1, 4.2) and any osteoporosis-related fracture (hazard ratio, 4.0; 95% CI: 1.1, 14.6). Conclusion Routine cardiac CT can be used to help measure thoracic bone mineral density (BMD) to identify individuals who have low BMD and a greater fracture rate. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Bredella in this issue.

Feasibility of Opportunistic Screening for Low Thoracic Bone Mineral Density in Patients Referred for Routine Cardiac CT.

Despite being a frequent and treatable disease, osteoporosis remains under-diagnosed worldwide. Our study aim was to characterize the bone mineral density (BMD) status in a group of patients with symptoms suggestive of coronary artery disease (CAD) with low/intermediate risk profile undergoing routine cardiac computed tomography (CT) to rule out CAD. This cross-sectional study used prospectively acquired data from a large consecutively included cohort. Participants were referred for cardiac CT based on symptoms of CAD. Quantitative CT (QCT) dedicated software was used to obtain BMD measurements in 3 vertebrae starting from the level of the left main coronary artery. We used the American College of Radiology cut-off values for lumbar spine QCT to categorize patients into very low (<80 mg/cm3), low (80-120 mg/cm3), or normal BMD (>120 mg/cm3). Analyses included 1487 patients. Mean age was 57 years (range 40-80), and 52% were women. The number of patients with very low BMD was 105 women (14%, 105/773) and 74 men (10%, 74/714). The majority of patients with very low BMD was not previously diagnosed with osteoporosis (87%) and received no anti-osteoporotic treatment (90%). Opportunistic screening in patients referred for cardiac CT revealed a substantial number of patients with very low BMD. The majority of these patients was not previously diagnosed with osteoporosis and received no anti-osteoporotic treatment. Identification of these patients could facilitate initiation of anti-osteoporotic treatment and reduce the occurrence of osteoporosis-related complications.

Evaluating Osteoporosis in Chronic Kidney Disease: Both Bone Quantity and Quality Matter.

Bone strength is determined not only by bone quantity [bone mineral density (BMD)] but also by bone quality, including matrix composition, collagen fiber arrangement, microarchitecture, geometry, mineralization, and bone turnover, among others. These aspects influence elasticity, the load-bearing and repair capacity of bone, and microcrack propagation and are thus key to fractures and their avoidance. In chronic kidney disease (CKD)-associated osteoporosis, factors traditionally associated with a lower bone mass (advanced age or hypogonadism) often coexist with non-traditional factors specific to CKD (uremic toxins or renal osteodystrophy, among others), which will have an impact on bone quality. The gold standard for measuring BMD is dual-energy X-ray absorptiometry, which is widely accepted in the general population and is also capable of predicting fracture risk in CKD. Nevertheless, a significant number of fractures occur in the absence of densitometric World Health Organization (WHO) criteria for osteoporosis, suggesting that methods that also evaluate bone quality need to be considered in order to achieve a comprehensive assessment of fracture risk. The techniques for measuring bone quality are limited by their high cost or invasive nature, which has prevented their implementation in clinical practice. A bone biopsy, high-resolution peripheral quantitative computed tomography, and impact microindentation are some of the methods established to assess bone quality. Herein, we review the current evidence in the literature with the aim of exploring the factors that affect both bone quality and bone quantity in CKD and describing available techniques to assess them.

Coronary Calcium Score May Replace Cardiovascular Risk Factors as Primary Risk Stratification Tool Before Kidney Transplantation.

BACKGROUND: Cardiac evaluation before kidney transplantation is recommended, but no unequivocal screening strategy has yet been identified. We investigated if coronary artery calcium score (CACS) can replace cardiovascular risk factor assessment in selection of kidney transplantation candidates for cardiac evaluation and the choice of noninvasive modality for diagnosing obstructive coronary artery disease (CAD). METHODS: We conducted a prospective study of 167 patients referred for pretransplantation cardiac evaluation. Patients underwent risk factor assessment, CACS, coronary computed tomography angiography (CCTA), single-photon emission computed tomography (SPECT), and invasive coronary angiography. In total, 138 patients completed all diagnostic tests. RESULTS: In patients with CAD (22%), the number of risk factors and CACS score were higher than that in patients without CAD. The accuracy evaluated by the receiver-operating characteristic curve was higher for CACS than for risk factors, 0.85 versus 0.71 (P = 0.01). Adding CACS to the risk factor increased correct categorical net reclassification (0.58, P < 0.0001). Combining risk factors (≥3) with SPECT to identify patients with obstructive CAD resulted in less sensitivity (47% vs 80%) and higher specificity (94% vs 74%), compared with CCTA. In patients with low CACS (<400), SPECT had a lower sensitivity than CCTA (60% versus 80%) but the same specificity (80%). In patients with high CACS (≥400), SPECT had lower sensitivity than CCTA (50% vs 100%) and higher specificity (88% vs 8%). CONCLUSIONS: In kidney transplantation candidates, CACS outperformed risk factor assessment for predicting obstructive CAD and is a better tool for selecting patients and guiding the choice of noninvasive diagnostic modality in CAD.