MO568STATIC PARAMETERS OF HISTOMORPHOMETRY FOR THE EVALUATION OF BONE TURNOVER IN RENAL OSTEODYSTROPHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hanne Skou Jørgensen ◽  
Geert Behets ◽  
Patrick D'Haese ◽  
Pieter Evenepoel
Keyword(s):  
Bone Turnover ◽  
Diagnostic Accuracy ◽  
Renal Osteodystrophy ◽  
Bone Biopsy ◽  
Bone Formation Rate ◽  
Suitable Alternative ◽  
Predictive Values ◽  
Bone Biopsies ◽  
Low Bone Turnover ◽  
Tetracycline Labeling

Abstract Background and Aims A full histomorphometric analysis of a transiliac bone biopsy with prior tetracycline labeling remains the gold standard to diagnose renal osteodystrophy. Bone turnover is primarly evaluated by the dynamic parameter bone formation rate, calculated from the incorporation of tetracycline in bone. In cases of failed tetracycline labels, however, an evaluation of bone turnover based on static parameters is warranted. This study investigates the diagnostic accuracy of static histomorphometric parameters for the diagnosis of high and low bone turnover. Method Bone biopsies with prior tetracycline labeling of sufficient quality for a full histomorpometric analysis were included (n = 205). Mean age of participants was 56±13 years, 67% were men, and 22% had diabetes mellitus. Diagnostic accuracy of static histomorphometric parameters for bone turnover was evaluated by area under the receiver operator characteristics curve (AUC) statistics, against the full set of static and dynamic histomorphometric parameters. The cohort was randomly split to allow calculation of optimal diagnostic cutoffs in an exploration cohort (n=105), with subsequent validation in a separate subset of patients (n=100). Results All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover (p < 0.01), and all were significant predictors of both high and low bone turnover (Figure 1). Calculated optimal cutoffs and their sensitivities and specificities in the validation cohort are shown in Table 1. Diagnostic accuracy was very good for high turnover, as the combination of presence of fibrosis with ObPm>5.4%, OcPm>1.5%, and OAr>2.4% provided a correct diagnosis in 94% of patients, with positive (PPV) and negative (NPV) predictive values of 80% and 96%, respectively. Using the same predefined combination, an accuracy of 80% was achieved for low turnover (no fibrosis, ObPm≤1.9% OcPm≤0.9% and OAr≤1.6%), with a PPV of 71% and a NPV of 82%. Conclusion Static histomorphometric parameters provide an acceptable alternative for the diagnosis of high and low bone turnover. In the absence of successful tetracycline labeling, the proposed cutoffs may provide a suitable alternative for the evaluation of bone turnover in renal osteodystrophy.

scholarly journals Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal Osteodystrophy

2018 ◽  
Vol 29 (5) ◽  
pp. 1557-1565 ◽  
Author(s):  
Syazrah Salam ◽  
Orla Gallagher ◽  
Fatma Gossiel ◽  
Margaret Paggiosi ◽  
Arif Khwaja ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Diagnostic Accuracy ◽  
Renal Osteodystrophy ◽  
Bone Biopsy ◽  
High Bone Turnover ◽  
Biopsy Specimens ◽  
Biomarker Analysis ◽  
Low Bone Turnover ◽  
High Bone

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry.Methods We obtained fasting blood samples from 69 patients with CKD stages 4–5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD.Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.

scholarly journals SO07118F-SODIUM FLUORIDE POSITRON EMISSION TOMOGRAPHY AND BONE HISTOMORPHOMETRY - COMPARISON BETWEEN ONLY BONE TURNOVER -BASED AND EXPERT EVALUATION -BASED CLASSIFICATION OF RENAL OSTEODYSTROPHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Louise Caroline Aaltonen ◽  
Niina Koivuviita ◽  
Marko Seppänen ◽  
Inari Burton ◽  
Heikki Kröger ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Renal Osteodystrophy ◽  
Bone Disease ◽  
Bone Biopsy ◽  
Formation Rate ◽  
Adynamic Bone Disease ◽  
High Turnover ◽  
Bone Formation Rate ◽  
Adynamic Bone

Abstract Background and Aims The diagnosis and the differentiation of renal osteodystrophy (ROD) are challenging. Bone biopsy is the golden standard, but it is invasive and not available in every center. Bone turnover rate is defined by bone formation rate and/or activation frequency. Adynamic bone disease is defined as low turnover bone with reduced osteoblast- and osteoclast activities. Hyperparahyreoid bone disease or osteitis fibrosa is defined as high turnover bone with osteoclast- and osteoblast activities and fibrosis. 18F- Sodium Fluoride positron emission tomography (18F-NaF PET) is a noninvasive imaging technique that allows assessment of regional bone turnover. The aim was to assess how well bone turnover –based classification of ROD correlates with the classification determined by an expert histomorphometrist (HK), and how these correlate with 18F-NaF PET analysis Method A total of 24 dialysis patients underwent a 18F-NaF PET scan. Fluoride activity was measured at the anterior iliac crest and in the lumbar region. An iliac crest bone biopsy was obtained within 4 weeks from the PET-scan. The diagnosis of bone histomorphometry was determined based on turnover-mineralization-volume (TMV) classification. Firstly, bone turnover was assessed using bone formation rate and activation frequency. Secondly, also other histomorphometric parameters (eg. osteoid volume, osteoid surface, resorption surface, mineralized surface, osteoblast and osteoclast surfaces and peritrabecular fibrosis) were also taking into account for classification of ROD by a histomorphometrist. Results Based on bone turnover parameters only, 12% of the patients had high turnover and 64% low turnover. When the diagnosis of renal osteodystrophy was made by a histomorphometrist, 40% had hyperparathyreoid bone/osteitis fibrosa and 24% adynamic bone disease or ostemalasia. 18F-NaF PET´s sensitivity to recognize hyperparathyreoid bone disease was 80% end specificity 100% (cut-of value 0.055).18F-NaF PET´s sensitivity to recognize adynamic bone disease was 100% and specificity 61% (cut-of value of fluoride-activity 0.038) Conclusion 18F-NaF PET works well as a diagnostic tool, when the diagnosis of ROD is based on the histopathological evaluation. It remains unknown how variations in normal bone turnover rate can be detected in CKD patients by 18F-NaF PET and if treatment decisions of ROD can be made only based on bone turnover.

scholarly journals High Prevalence of Low Bone Turnover and Occurrence of Osteomalacia after Kidney Transplantation

2000 ◽  
Vol 11 (6) ◽  
pp. 1093-1099 ◽  
Author(s):  
MARIE-CLAUDE MONIER-FAUGERE ◽  
HANNA MAWAD ◽  
QUANLE QI ◽  
ROBERT M. FRIEDLER ◽  
HARTMUT H. MALLUCHE
Keyword(s):  
Kidney Transplantation ◽  
Bone Turnover ◽  
Formation Rate ◽  
Normal Serum ◽  
Bone Volume ◽  
Bone Lesions ◽  
Bone Surface ◽  
Bone Formation Rate ◽  
Bone Biopsies ◽  
Low Bone Turnover

Abstract. Kidney transplantation corrects most of the metabolic abnormalities that cause renal osteodystrophy. However, many transplanted patients develop osteoporosis and other bone lesions that are related, at least in part, to their immunosuppressive regimen. The precise histologic patterns of bone disease after transplantation are not well defined. In a study designed to investigate this issue, 57 adult posttransplant patients agreed to undergo bone biopsies and blood drawings. There were 32 men and 25 women, mean age 45 ± 2 yr, who had received a kidney transplantation 5.6 ± 0.8 yr before biopsy. History of bone pain, fractures, and avascular necrosis was found in 22, 12, and 7 patients, respectively. Serum creatinine was 1.68 ± 0.1 mg/dl, 21% of patients were hypercalcemic, 63.2% had elevated parathyroid hormone (PTH) (>65 pg/ml), and 91.2% had normal calcitriol levels. Cancellous bone volume/tissue volume was below normal compared to age- and gender-matched control subjects in 56.1% of patients. Bone turnover (activation frequency) was low in 45.6%, normal in 28.1%, and elevated in 26.3% of patients. Bone formation rate/bone surface was low in 59.7%, normal in 35%, and elevated in 5.3% of the patients. Erosion surface/bone surface was high in 21.1% of patients. Mineralization was prolonged in 87.5% of patients, including 9 patients with osteomalacia and 12 patients with focal osteomalacia. Cumulative and maintenance doses of prednisone and time elapsed since transplantation correlated negatively with bone volume and bone turnover (r= -0.32 to -0.59,P< 0.05 to 0.01), whereas cumulative doses of cyclosporine or azathioprine, age, gender, or serum PTH levels did not. Regression analysis identified prednisone as the main factor responsible for low bone volume and bone turnover (r= 0.54 andr= 0.43,P< 0.01). No factors were found to predict delayed mineralization. The present study shows that low bone volume, low bone turnover, and generalized or focal osteomalacia are frequent histologic features in transplanted patients. The effects of age, gender, PTH, and cyclosporine on bone volume and bone turnover are apparently overridden by the prominent effects of glucocorticoids. The prevalence of mineralization defect in the presence of normal serum levels of calcidiol and calcitriol suggests vitamin D resistance and deserves further study.

FC 076DIAGNOSTIC ACCURACY OF BONE TURNOVER MARKERS IN RENAL OSTEODYSTROPHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hanne Skou Jørgensen ◽  
Geert Behets ◽  
Etienne Cavalier ◽  
Patrick D'Haese ◽  
Pieter Evenepoel
Keyword(s):  
Bone Turnover ◽  
Kidney Transplant ◽  
Renal Osteodystrophy ◽  
Type I Collagen ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Predictive Values ◽  
Bone Biopsies

Abstract Background and Aims A transiliac bone biopsy is the gold standard for diagnosing renal osteodystrophy, but is not recommended as part of routine clinical workup due to its invasive nature. Suitable non-invasive alternatives have yet to be established. The aim of this study was to investigate the diagnostic accuracy novel biochemical markers of bone remodeling compared to that of biointact parathyroid hormone (PTH) for bone turnover as evaluated by histomorphometry. Method Protocolled bone biopsies were performed in end-stage kidney disease patients (ESKD, n = 80) and kidney transplant recipients (n = 119). Full-length (1-84) PTH, bone-specific alkaline phosphatase (BsAP), intact N-terminal propeptide of type I collagen (P1NP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were measured. Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC). Optimal diagnostic cutoffs were established in an exploration cohort (n=100), and subsequently validated in a separate subset of patients (n=99). Results Mean age was 55±13 years, two-thirds were men (67%), and 23% had diabetes mellitus. Post-transplant eGFR was 49 [IQR 39, 59] ml/min/1.73m². Bone turnover was low in 47 (24%), normal in 119 (60%), and high in 33 (17%) patients. All biomarkers differed significantly across categories of bone turnover (p &lt; 0.001). The AUC of biointact PTH for high turnover was 0.82 (0.73, 0.91), which was not significantly different from AUC values for BsAP, Intact P1NP, and TRAP5b (0.87, 0.90, and 0.86, respectively). AUC of biointact PTH for low turnover was 0.71 (0.63, 0.78), which was significantly lower than the values for BsAP, Intact P1NP, and TRAP5b (0.79, 0.83, and 0.79, respectively; p &lt; 0.05, all). Calculated optimal diagnostic cutoffs in the exploration cohort are shown in Table 1. Applying these cutoffs in the validation cohort revealed high negative predictive values for both high (92 - 96%) and low (82 - 90%) bone turnover. Positive predictive values were consistently low. Conclusion The diagnostic accuracies of BsAP, Intact P1NP and TRAP5b are sufficient to rule out both high and low bone turnover in CKD. Biointact PTH shows inferior performance, particularly in kidney transplant recipients.

scholarly journals P0885THE RELATIONSHIP BETWEEN BONE REGULATORY MARKERS AND BONE TURNOVER IN RENAL OSTEODYSTROPHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Syazrah Salam ◽  
Orla Gallagher ◽  
Fatma Gossiel ◽  
Arif Khwaja ◽  
Richard Eastell
Keyword(s):  
Bone Formation ◽  
Bone Turnover ◽  
Renal Osteodystrophy ◽  
Bone Biopsy ◽  
Formation Rate ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Resorption Marker ◽  
Bone Formation Rate ◽  
Bone Formation Markers ◽  
The Relationship

Abstract Background and Aims Renal osteodystrophy is common in advanced chronic kidney disease (CKD) patients and is characterized by abnormal bone turnover and mineralization. Parathyroid hormone (PTH) increases bone turnover through osteoblast and osteoclast activation. Osteoprotegerin (OPG) is a decoy receptor of receptor activator of nuclear factor kappa-β ligand and thus, inhibits osteoclast maturation. Meanwhile, sclerostin is an inhibitor of the Wnt signalling pathway and thus, inhibits osteoblast maturation. We aimed to assess the relationship between these bone regulatory markers and bone turnover as assessed by bone histomorphometry and bone turnover markers (BTMs). Method We recruited 43 CKD patients with eGFR&lt;30ml/min/1.73m2 or on dialysis. Fasting serum samples were analysed using Immunodiagnostic Systems automated assays (Boldon, UK) for intact PTH (iPTH) and BTMs such as bone alkaline phosphatase (bALP) and intact procollagen type 1 N-terminal propeptide (intact PINP) which are bone formation markers, and tartrate-resistant acid phosphatase 5b (TRAP5b) which is a bone resorption marker. OPG and sclerostin were analysed using manual ELISA by Biomedica (Vienna, Austria). Trans-iliac bone biopsy was performed after tetracycline labelling. Bone samples were analysed using quantitative histomorphometry. Normal bone turnover was defined as bone formation rate/bone surface (BFR/BS) of 18 - 38µm3/µm2/year. Spearman rank correlation was used to test the relationship between the variables. Results Median BFR/BS was 32.12 (IQR 17.76 – 48.25) um3/um2/year. 26% of patients had low and 40% had high bone turnover. iPTH and OPG were positively correlated with BFR/BS (rho = 0.42, p&lt;0.01 and rho = 0.36, p&lt;0.05 respectively). Sclerostin was not correlated with BFR/BS. Furthermore, sclerostin did not correlate with bALP and intact PINP whereas OPG correlated with TRAP5b (rho = 0.43, p&lt;0.01). iPTH correlated with bALP (rho = 0.62, p&lt;0.001), intact PINP (rho = 0.62, p&lt;0.001) and TRAP5b (rho = 0.50, p = 0.001). Conclusion Circulating levels of iPTH and OPG were modestly associated with bone turnover but sclerostin was not. There are likely to be bone regulators other than iPTH, OPG and sclerostin which regulate bone turnover in renal osteodystrophy.

scholarly journals The role of bone biopsy in the management of patients with renal osteodystrophy.

1994 ◽  
Vol 4 (9) ◽  
pp. 1631-1642
Author(s):  
H H Malluche ◽  
M C Monier-Faugere
Keyword(s):  
Renal Osteodystrophy ◽  
Bone Disease ◽  
Bone Biopsy ◽  
Bone Biopsies ◽  
Renal Bone Disease ◽  
Tetracycline Labeling ◽  
Perceived Constraints ◽  
Bone Abnormalities

Renal osteodystrophy is not a uniform disease. Therefore, knowledge of the underlying bone abnormalities is essential in deciding specific therapeutic regimens. To date, however, there is no unequivocal noninvasive means with which to define bone abnormalities accurately. The best tool remains mineralized bone histology requiring bone biopsies. Despite recent technical improvements, this technique is underused because of perceived constraints. This article outlines the procedures necessary for increasing the value of bone biopsies, such as tetracycline labeling, and various biopsy techniques and their potential complications. Bone biopsies provide important information on precisely the type of renal bone disease affecting patients: (1) predominant hyperparathyroid bone disease; (2) low-turnover uremic osteodystrophy, encompassing osteomalacic and adynamic renal bone disease; and (3) mixed uremic osteodystrophy, consisting of mild to moderate hyperparathyroid bone disease and defective mineralization. Also, the degree of the severity of the lesions may be assessed. Finally, the presence and quantity of aluminum deposition in bone can be demonstrated. The determination of aluminum overload is needed before the initiation of any therapeutic regimens because it is well known that potentially serious complications can occur with current treatments such as vitamin D therapies, desferoxamine administration, or parathyroidectomy.

Prospective Evaluation of the Bone Anabolic Effect of Bortezomib in Relapsed Multiple Myeloma (MM) Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2719-2719 ◽  
Author(s):  
Maurizio Zangari ◽  
Federica Cavallo ◽  
Larry Suva ◽  
Joshua Dilley ◽  
Guido Trico ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Biopsy ◽  
Single Agent ◽  
Bone Architecture ◽  
Entire Study ◽  
Osteoblast Activity ◽  
Bone Biopsies ◽  
Tetracycline Labeling

Abstract Bortezomib (B) has been shown to increase osteoblast activity and inhibit osteoclast formation, thus promoting bone formation. We have previously reported a correlation between increased alkaline phosphatase (ALP) and the response to B in patients with MM. We now report results of a detailed prospective study examining the skeletal effects of B treatment in MM patients using histomorphometry, micro computed tomography (microCT) and markers of bone metabolism. Methods: Single agent B (1.3 mg/m2 patients 1–10; 1mg/m2 patient 11–20), was administered on days 1, 4, 8 and 11 on a 21 day intervals for a total of 3 cycles; no patients were receiving concurrent bisphosphonates or steroids during the entire study period. The dynamic indices of bone turnover were prospectively evaluated via tetracycline labeling prior to transiliac bone biopsies obtained at baseline and after 3 cycles of treatment. Biopsy specimens were examined by high-resolution microCT prior to histomorphometric analyses. Architectural parameters such as bone volume/total volume (BVTV), trabecular number (TbN), and thickness (Tb.Th) were recorded. Osteocalcin, and alkaline phosphatase on days 1,4,8,11 were measured before and after each B dose and every 4 hours thereafter, daily for the other days of the treatment cycle. Results: Histomorphometric analyses were compared in 7 of the 11 patients who completed the trial. All 11 patients underwent bone biopsy at baseline nine of those 11 at the end of the study (2 samples were not adequate). Baseline BV/TV values ranged from 13% to 80%. After 3 cycles of B treatment % increase (mean 37%) in BV/TV was shown in 6 of 7 patients (P<0.034). Tb.Th was also increased from baseline (range 20%–456%) in 5 of 7 patients (71%) who responded to B. Histological bone histomorphometry demonstrated a lack of osteoid formation and osteoblast activity at baseline and a marked increased in osteoid and osteoblast numbers on trabecular and cortical bone surface following B treatment. Tetracycline incorporation into bone was observed in only 2 of 11 of patients (18%) at baseline, reflecting the extremely low levels of bone turnover in MM patients prior to treatment. However, post-B tetracycline labeling was observed in 7 of 11 (63%) samples (p<0.03; baseline vs post treatment score changes), reflecting the dramatic increases in bone turnover elicited by B treatment. Interestingly, after B treatment, the rate of bone formation was accelerated in the 2 patients with measurable baseline tetracycline labeling. Baseline osteocalcin values were below the reference intervals (11–50 ng/ml) in 10 of 11 patients but increased in 9 of 11 patients at the end of the third B cycle. Overall osteocalcin changes increased from baseline by 403% (p<0.037). BALP ranged from 4.5 to 48.4 ug/l at baseline and increased in 6 of 10 patients following B treatment. Conclusion: In this first prospective single agent B study we demonstrate that even a short course (3 cycles or 12 doses) of B treatment has a significant and potent anabolic bone effect in MM patients, demonstrated by serum turnover markers, micro-CT measures of bone architecture and by static and dynamic histomorphometry.

FC 124PATTERNS OF RENAL OSTEODYSTROPHY ONE YEAR AFTER KIDNEY TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hanne Skou Jørgensen ◽  
Geert Behets ◽  
Patrick D'Haese ◽  
Pieter Evenepoel
Keyword(s):  
Kidney Transplantation ◽  
Bone Turnover ◽  
Kidney Transplant ◽  
Renal Osteodystrophy ◽  
Bone Disease ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Steroid Dose ◽  
Bone Biopsies

Abstract Background and Aims Bone disease after kidney transplantation is an issue of growing concern, as prolonged graft survival and older age of recipients necessitate focus on long-term health burdens such as osteoporosis and fractures. Pre-existing type of renal osteodystrophy, post-transplant immunosuppressive treatment, and de novo disturbances of mineral metabolism all contribute to bone disease in kidney transplant recipients. The current pattern of renal osteodystrophy after kidney transplantation is not well characterized. This study reports histomorphometric findings of protocolled bone biopsies in a large cohort of kidney transplant recipients 1 year post-transplant. Method Histomorphometric analysis of transiliac bone biopsies with prior tetracycline labelling was performed in 141 kidney transplant recipients. Biochemical measurements included bioactive parathyroid hormone (PTH), total calcium, phosphate, calcidiol, bicarbonate, and sclerostin. Kruskal-Wallis and Wilcoxon signed rank tests were used to evaluate differences across categories and between groups, respectively. Stepwise multivariate linear regression was performed to identify key demographic and biochemical determinants of bone turnover (bone formation rate, BFR), mineralization (mineralization lag time, Mlt), and volume (Bone area, BAr). Results Mean age was 57±11 years, 71% were men, and all were Caucasian. Mean eGFR was 49±16 (range 19 to 106) ml/min/1.73 m². Hyperparathyroidism (PTH &gt; 1.5xUNL) was seen in 48%, hypercalcemia (&gt;10.3 mg/dL) in 18%, hypophosphatemia (&lt;2.3 mg/dl) in 12%, and vitamin D deficiency (&lt;15 ng/mL) in 4% of patients. Categorization of bone turnover, mineralization, and volume is shown in Figure 1. Bone turnover was normal in the vast majority (71%). Patients with low turnover (26%) had received a higher cumulative steroid dose (2.78 vs 2.34g in low vs non-low turnover; p=0.02). Patients with delayed mineralization (16%) were younger (52 vs 58 yrs, p=0.02) and had received a higher cumulative steroid dose (2.85 vs 2.36g, p=0.003). They had higher levels of PTH (124 vs 53 ng/L, p&lt;0.001), and lower levels of phosphate (2.68 vs 3.18 mg/dL, p&lt;0.001), calcidiol (29 vs 37ug/L, p=0.02), bicarbonate (21.3 vs 23.3 mmol/L, p=0.004), and sclerostin (493 vs 594 pg/mL, p=0.03) compared to patients with normal mineralization. Patients with low bone volume tended to be older (61 vs 56 years, p=0.07). Independent determinants of BFR were PTH (β=0.68, p&lt;0.001) and cumulative steroid dose (β = -0.22, p=0.02). Determinants of Mlt were phosphate (β=-0.48, p=0.001) and cumulative steroid dose (β=0.18, p=0.004), and determinants of BAr were age (β=-0.15, p=0.002), and BMI (β=0.33, p=0.002). Conclusion Bone turnover is normal in the majority of kidney transplant recipients at 1 year post-transplant, despite a high prevalence of hyperparathyroidism. Low levels of bicarbonate, phosphate, and calcidiol may contribute to delayed bone mineralization in kidney transplant recipients.

scholarly journals A Comparison of the Effects of Raloxifene and Estrogen on Bone in Postmenopausal Women1

2000 ◽  
Vol 85 (6) ◽  
pp. 2197-2202
Author(s):  
Karen M. Prestwood ◽  
Michele Gunness ◽  
Douglas B. Muchmore ◽  
Yili Lu ◽  
Mayme Wong ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Biochemical Markers ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Markers Of Bone Turnover ◽  
Bone Biopsies ◽  
Hip Bmd ◽  
Total Body

Raloxifene HCl, a selective estrogen receptor modulator, has been shown to increase bone mineral density (BMD) and decrease biochemical markers of bone turnover in postmenopausal women without stimulatory effects on the breast and uterus. However, it is not known whether the changes in BMD and bone turnover are associated with changes at the tissue level, nor how changes with raloxifene compare with estrogen. In this randomized, double blind study, we evaluated the effects of raloxifene (Evista, 60 mg/day) or conjugated equine estrogens (CEE; Premarin, 0.625 mg/day) on bone architecture, bone turnover, and BMD. Iliac crest bone biopsies were obtained at baseline and at the end of the study after double tetracycline labeling and were analyzed for standard histomorphometric indexes. Serum and urinary biochemical markers of bone turnover were measured at baseline and at 4, 10, 18, and 24 weeks of treatment. Total body, lumbar spine, and hip BMD were measured at baseline and at the end of the study by dual energy x-ray absorptiometry. Activation frequency and bone formation rate/bone volume were significantly decreased from baseline in the CEE, but not in the raloxifene, group. Bone mineralization did not change in either group. Most markers of bone resorption and formation decreased in both groups, but to a greater degree in the CEE group (P &lt; .05). Total body and lumbar spine BMD increased from baseline in both groups, with a greater increase in the CEE group (P&lt; 0.05). Hip BMD significantly increased from baseline in the raloxifene group, but the change was not different from that in the CEE group. These results suggest that raloxifene reduces bone turnover and increases bone density, although to a lesser extent than CEE. Thus, raloxifene is an alternative to CEE for the prevention and treatment of osteoporosis in postmenopausal women.

scholarly journals SO070THE SPECTRUM OF RENAL OSTEODYSTROPHY IN PREVALENT PERITONEAL DIALYSIS PATIENTS IN 21ST CENTURY - A HISTOMORPHOMETRIC ANALYSIS OF BONE BIOPSIES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Luciano Pereira ◽  
Juliana Magalhães ◽  
Luís Mendonça ◽  
Hugo Diniz ◽  
Maria João Sousa ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Vascular Calcification ◽  
Renal Osteodystrophy ◽  
Frequent Pattern ◽  
Diabetic Patients ◽  
Histomorphometric Analysis ◽  
Bone Formation Rate ◽  
Susceptible Population ◽  
X Ray ◽  
Bone Biopsies

Abstract Background and Aims The spectrum of renal osteodystrophy (ROD) in peritoneal dialysis (PD) patients remains to be clarified. Most studies are old and the results inconsistent. Also there were changes in clinical practice that may have influenced the bone histology in PD patients. Method In order to characterize ROD in prevalent PD population, we performed tetracycline-labelled bone biopsies in 49 PD patients with histomorphometric analysis according KDIGO guidelines. Exclusion criteria: history of kidney transplant, hemodialysis, treatment with agents interfering in bone metabolism (for example bisphosphonates). Hands and pelvis x-ray were performed to evaluate vascular calcification (VC) and to calculate the Adragão score. All patients were treated with biocompatible PD solutions, with calcium concentration of 1.25 mmol/L. Results Forty-nine patients participated in the study, with 32 biopsies analyzed so far. Mean age was 52.4±10.9 years, 16 male, 6 with diabetes mellitus, 23 on manual PD, median time on PD was 22.1 (3-61) months. Mean calcium, phosphate and PTH were 9.2±0.5 mg/dL, 4.9±1.0 mg/dL and 489.87±227.8 pg/mL, respectively. Vascular calcification was detected in 29% of patients and mean Adragão score was 1.13. Essential histomorphometric and selected data is represented in table 1: Bone volume (BV) tended to be lower in diabetics - 17.1% (10.1-23.1) compared with non-diabetics – 22.6% (12.7-41.4) (p=0.07). Median bone formation rate (BFR) tended to be lower - 21.39 µm3/µm2/y (8.2-53.2) in diabetic patients than in non-diabetics - 28.63 µm3/µm2/y (3.5-89.77) (p=0.80). PTH levels also tended to be lower in diabetics – 384.8 pg/mL compared to non-diabetics – 514.1 pg/mL (p=0.14). BV tended to be lower in patients with VC – 19.1% (10.1-27) compared with patients without VC - 22.6% (12.7-41.4) (p=0.23). VC was detected on x-ray in all 6 patients with diabetes and only in 11.5% (3 in 26) of non-diabetic patients. Conclusion Similar to previous reports, the most frequent ROD pattern was ABD. However, PD patients with ABD had mean PTH of 405 pg/mL, a value well within the recommended KDIGO targets. This reinforces PTH as a far from ideal marker of bone turnover and suggests different targets for PTH levels in this seemingly highly susceptible population to ABD even when treated with low calcium dialysate. The proportion of patients with normal bone was higher than previously published. This finding can be explained by differences in the classification of ROD and prescription of biocompatible PD solutions in all patients. Diabetic patients tended to have lower BV and BFR. This finding is not surprising considering osteoblastic toxicity caused by advanced glycation end products. Also diabetic patients have a state of relative hypoparathyroidism. In conclusion, the most frequent pattern was ABD. Diabetic patients on PD may be a different subgroup.

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