Assessment of Bone Mineral Density From a Computed Tomography Topogram of Photon-Counting Detector Computed Tomography-Effect of Phantom Size and Tube Voltage.

PURPOSE: The aim of this study was to assess the accuracy and impact of different sizes and tube voltages on bone mineral density (BMD) assessment using a computed tomography (CT) topogram acquired with photon-counting detector CT in an osteopenic ex vivo animal spine. MATERIALS AND METHODS: The lumbar back of a piglet was used to simulate osteopenia of the lumbar spine. Five fat layers (each with a thickness of 3 cm) were consecutively placed on top of the excised spine to emulate a total of 5 different sizes. Each size was repeatedly imaged on (A) a conventional dual-energy x-ray absorptiometry scanner as the reference standard, (B) a prototype photon-counting detector CT system at 120 kVp with energy thresholds at 20 and 70 keV, and (C) the same prototype system at 140 kVp with thresholds at 20 and 75 keV. Material-specific data were reconstructed from spectral topograms for B and C. Bone mineral density was measured for 3 lumbar vertebrae (L2-L4). A linear mixed-effects model was used to estimate the impact of vertebra, imaging setup, size, and their interaction term on BMD. RESULTS: The BMD of the lumbar spine corresponded to a T score in humans between -4.2 and -4.8, which is seen in osteoporosis. Averaged across the 3 vertebrae and 5 sizes, mean BMD was 0.56 ± 0.03, 0.55 ± 0.02, and 0.55 ± 0.02 g/cm2 for setup A, B, and C, respectively. There was no significant influence of imaging setup (P = 0.7), simulated size (P = 0.67), and their interaction term (both P > 0.2) on BMD. Bone mineral density decreased significantly from L2 to L4 for all 3 setups (all P < 0.0001). Bone mineral density was 0.59 ± 0.01, 0.57 ± 0.01, and 0.52 ± 0.02 g/cm2 for L2, L3, and L4, respectively, for setup A; 0.57 ± 0.02, 0.55 ± 0.01, and 0.53 ± 0.01 g/cm2 for setup B; and 0.57 ± 0.01, 0.55 ± 0.01, and 0.53 ± 0.01 g/cm2 for setup C. CONCLUSION: A single CT topogram acquired on photon-counting detector CT with 2 energy thresholds enabled BMD quantification with similar accuracy compared with dual-energy x-ray absorptiometry over a range of simulated sizes and tube voltages in an osteopenic ex vivo animal spine.

Positive Effect of Teriparatide on Areal Bone Mineral Density in Young Women with Anorexia Nervosa: A Pilot Study.

The present pilot study investigated the effect of Teriparatide 1-34 rh-PTH (TPT) in young women diagnosed with anorexia nervosa (AN), and markedly compromised Bone Mineral Density (BMD). Patients were included who had (i) very low BMD (defined as Z-Score < - 2.5 or T-Score < - 2.5 if available) in at least one of the assessed localizations (lumbar spine L1-L4, total hip, femoral neck) without any previous fragility fracture; or (ii) low bone mineral density (defined as Z-Score < - 1.5 or T-Score < - 1.5 if available) in at least one of the assessed localizations (lumbar spine L1-L4, total hip, femoral neck) and at least one previous fragility fracture. Ten patients with an age range of 21-33 were recruited and their bone outcome was assessed after 12, 18, and 24 months. After 24 months of TPT treatment, BMD improved by 13.5% in the spine, 5.0% in the femoral neck, and 4.0% in the hip. Radius cortical bone density (- 2.6%) and radius cortical thickness (- 6.4%) decreased significantly, while in tibia there was no significant decrease. Neither in radius nor in tibia a significant change in trabecular bone parameters occurred. During the treatment, the patients' body weight did not increase significantly. Patients did not experience severe adverse events; only mild side effects were observed. Although these results emerged from a single-arm prospective study, it seems that AN patients with a severely compromised bone situation can benefit from TPT. Larger studies are needed to ascertain the effect of this promising substance.

Bone Mineral Density Quantification from Localizer Radiographs: Accuracy and Precision of Energy-integrating Detector CT and Photon-counting Detector CT.

Background Bone mineral density (BMD) could be derived from CT localizer radiographs and could potentially enable opportunistic osteoporosis screening. Purpose To assess the accuracy and precision of BMD measurement using two localizer radiographs obtained with energy-integrating detector CT and a single localizer radiograph obtained with photon-counting detector CT. Materials and Methods A calibration phantom and a porcine phantom with lumbar vertebrae were imaged with a dual-energy x-ray absorptiometry (DXA) scanner, a clinical energy-integrating detector CT scanner, and a prototype photon-counting detector CT scanner. Two localizer radiographs at different combinations of tube voltages were obtained with energy-integrating detector CT, and one localizer radiograph was obtained with photon-counting detector CT using different energy thresholds. BMD was calculated for all three approaches and compared with the known specifications in the calibration phantom. In the animal phantom, BMDs from both CT systems were compared with those from the DXA scanner (the reference standard). Accuracy was defined as the measurement error of BMD (ΔBMD), and precision was defined as the coefficient of variation (in percentage). Radiation doses were estimated. Nonparametric tests were applied. Results In the calibration phantom, ΔBMD was smaller with both CT systems compared with the DXA scanner (both P < .05). ΔBMD ranged from -5% to -1.8% for DXA, from -2.3% to -1.7% for energy-integrating detector CT, and from -1.6% to 1.6% for photon-counting detector CT. Precision (range, 0.3%-2.8%) was high for both CT systems. In the animal phantom, ΔBMD ranged from -0.6% to 0.1% for energy-integrating detector CT and from -0.1% to 0.6% for photon-counting detector CT, with no significant differences between CT systems (P = .65). The dose-area product in the animal phantom was 4.6 cGy ∙ cm2 for DXA, 3.5-11.5 cGy ∙ cm2 for energy-integrating detector CT, and 7.2-11.2 cGy ∙ cm2 for photon-counting detector CT, depending on tube voltage and energy threshold combination. Conclusion Experimental evidence suggests that bone mineral density measurements are accurate and precise using two localizer radiographs at different tube voltages from energy-integrating detector CT and a single localizer radiograph with different energy thresholds from photon-counting detector CT. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Pourmorteza in this issue.

Predictive Power of Bone Turnover Biomarkers to Estimate Bone Mineral Density after Kidney Transplantation with or without Denosumab: A post hoc Analysis of the POSTOP Study.

BACKGROUND: Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients. METHODS: Changes in BTMs - procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), ß-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr - at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D. RESULTS: Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment. CONCLUSIONS: Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.

Expert consensus on relevant risk predictors for the occurrence of osteoporotic fractures in specific clinical subgroups - Delphi survey.

BACKGROUND: There is an ongoing discussion about incorporating additional risk factors to established WHO fracture risk assessment tool (FRAX) to improve the prediction accuracy in clinical subgroups. We aimed to reach an expert consensus on possible additional predictive parameters for specific clinical subgroups. METHODS: Two-round modified Delphi survey: We generated a shortlist of experts from the authors' lists of the pertinent literature and complemented the list with experts known to the authors. Participants were asked to name possible relevant risk factors besides the FRAX-parameters for the occurrence of osteoporotic fractures. Experts specified these possible predictors for specific subgroups of patients. In the second round the expert panel was asked to weight each parameter of every subgroup assigning a number between one (not important) to ten (very important). We defined the threshold for an expert consensus if the interquartile range (IQR) of a predictor was ≤2. The cut-off value of the median attributed weights for a relevant predictor was set at ≥7. RESULTS: Eleven experts of seven countries completed both rounds of the Delphi. The participants agreed on nine additional parameters for seven categories. For the category "secondary osteoporosis", "older adults" and "nursing home patients", there was a consensus that history of previous falls was relevant, while for men and postmenopausal women, there was a consensus that the spine fracture status was important. For the group "primary and secondary osteoporosis" the experts agreed on the parameters "high risk of falls", "lumbar spine bone mineral density (BMD)" and "sarcopenia". CONCLUSION: This Delphi survey reached a consensus on various parameters that could be used to refine the currently existing FRAX for specific clinical situations or patient groups. The results may be useful for studies aiming at improving the predictive properties of instruments for fracture prediction.

Follow-Up of Bone Mineral Density Changes in de novo Kidney Transplant Recipients Treated with Two Doses of the Receptor Activator of Nuclear Factor κB Ligand Inhibitor Denosumab.

BACKGROUND: Studies in women with post-menopausal osteoporosis have shown that discontinuation of treatment with denosumab leads to an increased risk of vertebral fractures because of rebound bone turnover and rapid loss of bone mineral density (BMD). METHODS: In a post hoc analysis of the Prolia for Osteoporosis of Transplant Operated Patient study, we analyzed the effect of denosumab withdrawal on BMD changes. Twenty-five de novo kidney transplant recipients (KTR) who were treated for 1 year with 2 six-monthly doses of denosumab on top of standard treatment (daily calcium and vitamin D) were compared to a control group of 29 KTR who received standard treatment alone. BMD changes were analyzed by repeated dual-energy X-ray absorptiometry shortly after transplantation (baseline), after 6 and 12 months (active treatment phase) and after 2-6.5 years (follow-up phase). RESULTS: The average BMD at the lumbar spine declined markedly after discontinuation of treatment with denosumab but increased again thereafter. Thus, the average monthly change in lumbar spine BMD from month 12 onward was only 0.1 ± 2.8‰ in the denosumab group but 1.5 ± 1.9‰ in the control group (p = 0.021). The average monthly change in lumbar spine BMD from baseline to follow-up was similar in the control and denosumab group (1.1 ± 1.2‰ vs. 1.5 ± 2.4‰, p = 0.788). Similar results were seen at the total hip. CONCLUSIONS: In de novo KTR treated with 2 doses of denosumab, we detect a marked decrease in lumbar spine and hip BMD when denosumab is discontinued. Denosumab treatment should therefore not be discontinued without considering an alternative antiresorptive treatment.

[From Axial Spondyloarthritis to Osteoporosis - Spectrum of Skeletal Involvement in Inflammatory Bowel Diseases]. / Von Spondyloarthritis bis Osteoporose ­ Beteiligung des Skelettsystems bei chronisch entzündlichen Darmerkrankungen.

From Axial Spondyloarthritis to Osteoporosis - Spectrum of Skeletal Involvement in Inflammatory Bowel Diseases Abstract. Inflammatory bowel diseases (IBD) are frequently accompanied by non-inflammatory joint pain and inflammatory spondyloarthritides. Spondyloarthritides can restrict joint function and typically manifest with inflammatory back pain with nightly pain and morning stiffness that improves upon exercising. In other patients, small or large peripheral joints are predominantly involved. Treatment comprises pain medication including COX-II selective non-steroidal anti-inflammatory drugs (NSAID), since non-selective NSAID can aggravate IBD. For axial manifestations, physiotherapy and tumor necrosis factor (TNF) inhibitors are effective, while for peripheral manifestations steroid injections, sulfasalazine and TNF inhibitors are useful. Osteopenia and osteoporosis may result from inflammation, malabsorption and/or steroids. Long-lasting disease activity or steroid treatment should prompt osteoporosis screening. Adequate calcium and vitamin D intake must be ensured and treatment with bisphosphonates evaluated.

Relationship of Serum Bicarbonate Levels with 1-Year Graft Function in Kidney Transplant Recipients in Switzerland.

BACKGROUND: Metabolic acidosis (MA) is common in kidney transplant recipients (KTRs). Several studies have shown that MA is involved in the progression of chronic kidney disease. However, it is unclear if there is also a relationship between serum bicarbonate and graft function after kidney transplantation (KTx). We hypothesized that low serum bicarbonate is associated with a lower estimated glomerular filtration rate (eGFR) 1 year after KTx. METHODS: We performed a post hoc analysis of a single-center, open-label randomized trial in 90 KTRs and investigated the relationship of serum bicarbonate and graft function in the first year after KTx. RESULTS: Prevalence of MA was high after KTx (63%) and decreased to 28% after 1 year. Bicarbonate (20.6 ± 3.0 to 22.7 ± 2.7 mmol/L) increased in the first year after transplantation whereas eGFR (53.4 ± 15.8 to 56.9 ± 18.5 mL/min/1.73 m2) did not change significantly. Higher serum bicarbonate (p = 0.029) was associated with higher eGFR in the first year after KTx. CONCLUSION: Prevalence of MA is high in KTRs. In the first year after KTx, serum bicarbonate was positively correlated with eGFR, suggesting a potential role of MA in kidney graft function.

Effect of denosumab on trabecular bone score in de novo kidney transplant recipients.

BACKGROUND: Kidney transplant recipients (KTR) are at risk to lose bone mass. The trabecular bone score (TBS) represents a recently developed parameter of lumbar spine trabecular bone texture that correlates with the occurrence of fractures. METHODS: We analysed the 1-year changes in TBS in 44 de novo KTR that were randomized 1:1 to denosumab or no treatment. TBS was derived from dual energy X-ray absorptiometry and was correlated with 1-year areal bone mineral density (aBMD) changes at the lumbar spine and total hip. Correlations were also performed with parameters of peripheral bone microarchitecture and bone strength at the distal tibia and distal radius, as assessed by high-resolution peripheral quantitative computed tomography (HRpQCT) and micro-finite element analysis. RESULTS: The baseline TBS in KTR amounted to 1.312 ± 0.101, which is lower than the TBS of an age-matched normal control population (range 1.364-1.471). The TBS correlated positively with aBMD at the lumbar spine (Spearman's ρ = 0.56; P < 0.001) and total hip (ρ = 0.33; P < 0.05). The baseline TBS also correlated with HRpQCT-derived total (ρ = 0.49; P < 0.05) and trabecular volumetric BMD (ρ = 0.57; P < 0.01) and trabecular separation (ρ = -0.46; P < 0.05) at the tibia. Denosumab treatment led to an increase in TBS, paralleling the BMD changes at the lumbar spine. CONCLUSIONS: The TBS is a useful additional score of bone health, which may help to better define fracture risk. Treatment with denosumab led to improved trabecular bone texture in de novo KTR in addition to its beneficial effect on BMD.

Single-level vertebral kyphoplasty is not associated with an increased risk of symptomatic secondary adjacent osteoporotic vertebral compression fractures: a matched case-control analysis.

This matched case-control study compared the rate of symptomatic adjacent-level vertebral compression fractures (VCF) within 1 year in patients operatively treated with kyphoplasty to a control group of non-operatively treated VCFs. The adjacent-level fracture rate did not show a significant difference between groups. PURPOSE: To compare the rate of new symptomatic adjacent-level fractures within 1 year after an isolated osteoporotic vertebral compression fracture (VCF) treated by either kyphoplasty or non-operative treatment. METHODS: Patients aged ≥ 50 years with an isolated, fresh, and symptomatic osteoporotic VCF who were treated by kyphoplasty were compared to patients of similar age, gender, vertebral segment, and bone mineral density who were treated non-operatively (n = 98). A matched case-control analysis was conducted by retrospective chart review, and the rate of new adjacent-level symptomatic vertebral fractures, defined as occurring within two segments of the index fracture, within the first year was determined. RESULTS: Ninety-eight patients (66 female, aged 73.5, SD 9.7 years) were analyzed in this matched case-control study. The adjacent fracture rate within 1 year was not different between the kyphoplasty group and the non-operative group (20.4 vs 18.4%; McNemar, p = 1.0). The time to a new adjacent fracture after the index fracture was significantly shorter in the kyphoplasty (7, SD 8 weeks) versus non-operative group (22, SD 13 weeks). CONCLUSIONS: Patients with osteoporotic VCFs treated with kyphoplasty did not show an increased rate of additional symptomatic adjacent-level VCFs when compared to a non-operative control group matched for age, gender, fracture level, and bone mineral density. LEVEL OF EVIDENCE: Level III.

Food intake and energy expenditure in growing cats with and without a predisposition to overweight.

Overweight and obesity are multifactorial diseases caused by an imbalance in energy metabolism. An underlying genetic predisposition is often a factor in these conditions. In the cat breeding family of the Institute of Animal Nutrition at the Vetsuisse Faculty, University of Zurich, a segregating overweight phenotype with a genetic contribution was observed. From this breeding family, 26 kittens were followed from birth up to 8 months of age. During this time, food intake was measured using an automatic feeding station, and energy expenditure was investigated using indirect calorimetry at the ages of 4 and 6 months. Dual-energy X-ray absorptiometry (DEXA) was performed and blood glucose, leptin and insulin were measured at the ages of 4, 6 and 8 months. The kittens were also weighed daily for the first 2 weeks of life, every second day until weaning and once per week until 8 months of age. The body condition score (BCS) was evaluated monthly between 2 and 8 months of age. The main finding of this study is that a predisposition to overweight is connected to a higher food intake early in life, with no significant alterations in energy expenditure. The leptin blood levels were related to body fat percentage, and insulin sensitivity did not seem to be affected.

Osteoporosis drug treatment: duration and management after discontinuation. A position statement from the SVGO/ASCO.

Antiosteoporotic drugs are recommended in patients with fragility fractures and in patients considered to be at high fracture risk on the basis of clinical risk factors and/or low bone mineral density. As first-line treatment most patients are started with an antiresorptive treatment, i.e. drugs that inhibit osteoclast development and/or function (bisphosphonates, denosumab, oestrogens or selective oestrogen receptor modulators). In the balance between benefits and risks of antiresorptive treatment, uncertainties remain regarding the optimal treatment duration and the management of patients after drug discontinuation. Based on the available evidence, this position statement will focus on the long-term management of osteoporosis therapy, formulating decision criteria for clinical practice.

Normative values for CT-based texture analysis of vertebral bodies in dual X-ray absorptiometry-confirmed, normally mineralized subjects.

OBJECTIVES: To develop age-, gender-, and regional-specific normative values for texture analysis (TA) of spinal computed tomography (CT) in subjects with normal bone mineral density (BMD), as defined by dual X-ray absorptiometry (DXA), and to determine age-, gender-, and regional-specific differences. MATERIALS AND METHODS: In this retrospective, IRB-approved study, TA was performed on sagittal CT bone images of the thoracic and lumbar spine using dedicated software (MaZda) in 141 individuals with normal DXA BMD findings. Numbers of female and male subjects were balanced in each of six age decades. Three hundred and five TA features were analyzed in thoracic and lumbar vertebrae using free-hand regions-of-interest. Intraclass correlation (ICC) coefficients were calculated for determining intra- and inter-observer agreement of each feature. Further dimension reduction was performed with correlation analyses. RESULTS: The TA features with an ICC < 0.81 indicating compromised intra- and inter-observer agreement and with Pearson correlation scores r > 0.8 with other features were excluded from further analysis for dimension reduction. From the remaining 31 texture features, a significant correlation with age was found for the features mean (r = -0.489, p < 0.001), variance (r = -0.681, p < 0.001), kurtosis (r = 0.273, p < 0.001), and WavEnLL_s4 (r = 0.273, p < 0.001). Significant differences were found between genders for various higher-level texture features (p < 0.001). Regional differences among the thoracic spine, thoracic-lumbar junction, and lumbar spine were found for most TA features (p < 0.021). CONCLUSION: This study established normative values of TA features on CT images of the spine and showed age-, gender-, and regional-specific differences in individuals with normal BMD as defined by DXA.

Metabolic response to three different diets in lean cats and cats predisposed to overweight.

BACKGROUND: The existence of a genetic predisposition to obesity is commonly recognized in humans and rodents. Recently, a link between genetics and overweight was shown in cats. The goal of this study was to identify the effect of diet composition on plasma levels of glucose, insulin, free fatty acids and triglycerides in cats receiving different diets (high-carbohydrate, high-fat and high-protein diets). RESULTS: Insulin and leptin concentrations were significantly correlated with phenotype. Insulin levels were lower, whereas leptin levels were higher in cats predisposed to overweight. The other blood parameters were not correlated with phenotype. Intake of the high-carbohydrate diet resulted in higher insulin concentrations compared with the two other diets. Insulin levels were within the values described for non-obese cats in previous studies. CONCLUSIONS: There was no difference in metabolic response between the two groups. As the high-carbohydrate diet led to the highest insulin blood concentrations, it might be useful to avoid such diets in cats predisposed to overweight. In addition, even cats with genetically linked obesity can regain insulin sensitivity after weight loss.

Widely differing screening and treatment practice for osteoporosis in patients with inflammatory bowel diseases in the Swiss IBD cohort study.

Low bone mineral density (BMD) and osteoporosis remain frequent problems in patients with inflammatory bowel diseases (IBDs). Several guidelines with nonidentical recommendations exist and there is no general agreement regarding the optimal approach for osteoporosis screening in IBD patients. Clinical practice of osteoporosis screening and treatment remains insufficiently investigated.In the year 2014, a chart review of 877 patients included in the Swiss IBD Cohort study was performed to assess details of osteoporosis diagnostics and treatment. BMD measurements, osteoporosis treatment, and IBD medication were recorded.Our chart review revealed 253 dual-energy x-ray absorptiometry (DXA) scans in 877 IBD patients; osteoporosis was prevalent in 20% of tested patients. We identified widely differing osteoporosis screening rates among centers (11%-62%). A multivariate logistic regression analysis identified predictive factors for screening including steroid usage, long disease duration, and perianal disease; even after correction for all risk factors, the study center remained a strong independent predictor (odds ratio 2.3-21 compared to the center with the lowest screening rate). Treatment rates for patients with osteoporosis were suboptimal (55% for calcium, 65% for vitamin D) at the time of chart review. Similarly, a significant fraction of patients with current steroid medication were not treated with vitamin D or calcium (treatment rates 53% for calcium, 58% for vitamin D). For only 29% of patients with osteoporosis bisphosphonate treatment was started. Treatment rates also differed among centers, generally following screening rates. In patients with longitudinal DXA scans, calcium and vitamin D usage was significantly associated with improvement of BMD over time.Our analysis identified inconsistent usage of osteoporosis screening and underuse of osteoporosis treatment in IBD patients. Increasing awareness of osteoporosis as a significant clinical problem in IBD patients might improve patient care.

Infections in De Novo Kidney Transplant Recipients Treated With the RANKL Inhibitor Denosumab.

BACKGROUND: Infections are a major cause of morbidity and mortality in kidney allograft recipients. In this post hoc analysis of a randomized clinical trial which tested the effect of denosumab on bone mineral density, we assessed the impact of this drug on the incidence and severity of infections in the first year after kidney transplantation. METHODS: In this clinical trial, we randomized 90 de novo kidney transplant recipients shortly after transplantation to either denosumab on top of standard treatment (calcium and vitamin D) (n = 46), or to standard treatment alone (n = 44). Among all adverse events, we analyzed all infections that occurred within the first year after transplantation, and compared their incidence and severity in both groups. RESULTS: Overall, we identified more infections (n = 146) in the denosumab group than in the control group (n = 99). The most common infections were urinary tract infection (cystitis) (34.9% vs 25.2%), cytomegalovirus viremia (17.8% vs 24.2%), flu-like syndrome (11.6% vs 14.1%), polyoma (BK) viremia (8.2% vs 11.1%), and herpes simplex infections (5.5% vs 4.0%). Episodes of urinary tract infection (cystitis) occurred more often in the denosumab than in the control group (51 vs 25 episodes in 24 vs 11 patients, P = 0.008), whereas episodes of transplant pyelonephritis or urosepsis were not more frequent (3 vs 5 episodes). CONCLUSIONS: This post hoc analysis reveals that treatment with denosumab to prevent bone loss in first-year kidney transplant recipients was associated with more frequent episodes of urinary tract infections, whereas other infections occurred with similar frequency in both treatment groups.

Prediction of low bone mineral density in patients with inflammatory bowel diseases.

BACKGROUND: Low bone mineral density (BMD) remains a frequent problem in patients with inflammatory bowel diseases (IBD). There is no general agreement regarding osteoporosis screening in IBD patients. METHODS: Cases of low BMD and disease characteristics were retrieved from 3172 patients of the Swiss IBD cohort study. Multivariate logistic regression analysis was conducted for predictive modeling. In a subgroup of 877 patients, 253 dual-energy X-ray absorptiometry (DXA) scans were available for validation. RESULTS: Low BMD was prevalent in 19% of patients. We identified seven predictive factors: type of IBD, age, recent steroid usage, low body mass index, perianal disease, recent high disease activity and malabsorption syndrome. Low BMD could be predicted with a sensitivity of 79% and a specificity of 64%, a positive predictive value (PPV) of 35% and a negative predictive value (NPV) of 93%. The area under the curve of the receiver operating characteristics was 0.78. In the validation cohort we calculated a PPV of 26% and an NPV of 88%. CONCLUSION: We provide a comprehensive analysis of risk factors for low BMD and propose a predictive model with seven clinical variables. The high NPV of models such as ours might help in excluding low BMD to prevent futile investigations.

Effect of Denosumab on Peripheral Compartmental Bone Density, Microarchitecture and Estimated Bone Strength in De Novo Kidney Transplant Recipients.

BACKGROUND/AIMS: In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known. METHODS: The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14). RESULTS: Consistent with the full trial findings, denosumab reduced biomarkers of bone turnover, and significantly increased aBMD at the lumbar spine (median difference of 4.7%; 95% confidence interval [CI] 2.6 - 7.8; p<0.001). Bone quality as assessed by total and cortical volumetric bone mineral density (Tot. vBMD, Ct.vBMD) and cortical thickness (Ct.Th) increased significantly at the tibia, while changes at the radius were less pronounced. The trabecular volumetric BMD (Tb.vBMD), thickness (Tb. Th), separation (Tb.Sp) and number (Tb.N) and the cortical porosity (Ct.Po) at the tibia and the radius did not significantly change in both treatment groups. Micro-finite element analysis (µFEA) showed that bone stiffness increased significantly at the tibia (median difference 5.6%; 95% CI 1.8% - 9.2%; p=0.002) but not at the radius (median difference 2.9%, 95% CI -3.7% - 9.1%; p=0.369). Likewise, failure load increased significantly at the tibia (median difference 5.1%; 95% CI 2.1% - 8.1%; p=0.002) but not at the radius (median difference 2.4%, 95% CI -3.2% - 8.5%; p=0.336). CONCLUSIONS: These findings demonstrate that denosumab improves bone density and bone quality in first-year kidney transplant recipients at risk to develop osteoporosis.