Recommend-Response and Complications Comparing Radiofrequency Ablation Versus Parathyroidectomy for Secondary Hyperparathyroidism in Dialysis Patients

Introduction : To compare the efficacy and safety of ultrasound(US)-guided radiofrequency ablation (RFA) and parathyroidectomy (PTX) in the treatment of secondary hyperparathyroidism (SHPT). Methods In this retrospective study, we divided patients into PTX (n=53) and RFA (n=47) groups. The primary outcomes were the proportion of patients achieved the target range of iPTH concentrations(124-558pg/mL) and the long-term prognosis. The secondary outcomes were the differences in the changes of iPTH, calcium, and phosphorus over time and the incidence of adverse events. Results There was rarely difference in baseline characteristics between the two groups. Primary outcomes: The iPTH concentrations of 25.8% of patients in the PTX group and 51.3% of the RFA group were within the recommended range at the endpoint (P=0.031). Survival analysis revealed that the difference in all-cause mortality and cumulative response rate between the two groups was not statistically significant (P=0.902, P=0.141, respectively). Secondary outcomes: The iPTH concentrations in PTX group and RFA group dropped sharply after treatment and were 82.30±163.21pg/mL and 279.96±306.57pg/mL (P<0.001). There was no difference in the trend of iPTH, calcium, and phosphorus levels between the two groups over time(P>0.05). In addition, the incidence of infection and the hospital stay in the RFA group were significantly less. And preoperative bone-specific alkaline phosphatase concentration was a risk factor for postoperative hypocalcemia. Conclusion US-guided RFA was minimally invasive and no less than PTX in terms of cumulative response rate and complications in the treatment of severe SHPT in maintenance dialysis patients and may be used as an alternative technique to PTX, which need further studies to confirm.

The Source Matters–Effects of High Phosphate Intake from Eight Different Sources in Dogs

Elevated serum phosphate concentrations are an established risk factor for cardiovascular disease and mortality in chronic kidney disease in various species. Independent associations of other parameters of phosphorus metabolism, such as phosphorus intake from different sources and serum concentrations of phosphorus, as well as parameters involved in the regulation, such as parathyroid hormone (PTH) or markers of bone turnover, have been studied in less detail. Therefore, the serum kinetics of phosphate, PTH, and the bone resorption marker bone-specific alkaline phosphatase (BAP) were investigated after 18 days of feeding a control diet and diets supplemented with eight different organic and inorganic phosphate sources aiming at 1.8% phosphorus per dry matter and calcium to phosphorus ratio between 1.3 and 1.7 to 1. Eight healthy beagle dogs (f/m, 2–4 years, 12.9 ± 1.4 kg body weight) were available for the trial. Highly significant differences in the serum kinetics of phosphorus, PTH, and BAP with the highest postprandial levels after feeding highly water-soluble sodium and potassium phosphates were found. We conclude that the use of certain inorganic phosphates in pet food is potentially harmful and should be restricted.

Gujiansan Ameliorates Avascular Necrosis of the Femoral Head by Regulating Autophagy via the HIF-1α/BNIP3 Pathway

Background. Clinically, the traditional Chinese medicine compound Gujiansan has been widely used in the treatment of steroid-induced avascular necrosis of the femoral head (SANFH). The present study aimed to investigate the mechanisms underlying the therapeutic effect of Gujiansan. Methods. A rat model of SANFH was established by the injection of dexamethasone (DEX) at a high dosage of 25 mg/kg/d. Then, Gujiansan was intragastrically administered for 2 weeks, 4 weeks, and 8 weeks, and histological examination of the femoral head was performed. The expression levels of related mRNAs and proteins were analyzed by qRT-PCR, Western blotting, and immunohistochemistry, and the levels of bone biochemical markers and cytokines were detected with ELISA kits. Results. Gujiansan administration ameliorated SANFH and induced the expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), LC3, and Beclin-1 in the rat model in a dose- and time-dependent manner, and Gujiansan promoted osteocalcin secretion at the femoral head. In addition, Gujiansan increased the levels of bone formation- and bone resorption-specific markers (osteocalcin (OC), bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase-5b (TRACP-5b), N-terminal telopeptides of type I collagen (NTX-1), and C-terminal telopeptide of type I collagen (CTX-1)) and decreased the levels of proinflammatory cytokines (TNF-α, IL-6, and CRP) in a dose- and time-dependent manner. Conclusions. Gujiansan accelerates the formation of a new bone, promotes the absorption of the damaged bone, inhibits the inflammatory response, induces autophagy of the femoral head via the HIF-1α/BNIP3 pathway, and ultimately ameliorates SANFH.

Bone turnover markers can predict healing time in medication-related osteonecrosis of the jaw

Objectives Medication-related osteonecrosis of the jaw (MRONJ) is a severe and difficult-to-treat adverse event of bone-modifying agents. Therefore predictive strategies determining patients at risk for a prolonged healing duration are needed to optimize treatment. Thus, the present study evaluates whether or not bone turnover markers can be used to predict the healing duration in MRONJ patients. Materials and methods The present study is a retrospective data analysis of patients suffering from MRONJ and positive histology for Actinomyces spp., who were identified at the General Hospital Vienna from 2014 to 2018. During the first visit, the patients’ demographics and levels of bone formation parameters were compiled. Healing times were analysed by Cox regression in dependence on these factors. Results A total of 52 patients were identified who fulfilled the inclusion criteria. The indication for bone-modifying agents was breast cancer (n = 21), prostate cancer (n = 14), multiple myeloma (n = 6) and other malignant diseases (n = 11). In 43 (82.7%) of our patients, we were able to document complete mucosal healing. Furthermore, patients who responded faster to therapy showed higher levels of C-telopeptide (P < 0.05), osteocalcin (P < 0.05) and bone-specific alkaline phosphatase (P < 0.05), but lower levels of 1.25-dihydroxyvitamin D (P < 0.05) than slower responding patients. No correlation was found regarding parathyroid hormone or calcitonin levels. Interestingly, patients who had a slower response were less likely to report dental procedures, but more likely to report a history of chemotherapy. Conclusion CTX and osteocalcin levels may be used for predicting healing duration for MRONJ.

Acute Response of Sclerostin to Whole-body Vibration with Blood Flow Restriction

Blood flow restriction may augment the skeletal response to whole-body vibration. This study used a randomised, crossover design to investigate the acute response of serum sclerostin and bone turnover biomarkers to whole-body vibration with blood flow restriction. Ten healthy males (mean±standard deviation; age: 27±8 years) completed two experimental conditions separated by 7 days: (i) whole-body vibration (10 1-minute bouts of whole-body vibration with 30 s recovery) or (ii) whole-body vibration with lower-body blood flow restriction (10 cycles of 110 mmHg inflation with 30 s deflation during recovery). Fasting blood samples were obtained immediately before and immediately after exercise, then 1 hour, and 24 hours after exercise. Serum samples were analysed for sclerostin, cross-linked C-terminal telopeptide of type I collagen, and bone-specific alkaline phosphatase. There was a significant time × condition interaction for bone-specific alkaline phosphatase (p=0.003); bone-specific alkaline phosphatase values at 24 hours post-exercise were significantly higher following whole-body vibration compared to combined whole-body vibration and blood flow restriction (p=0.028). No significant time × condition interaction occurred for any other outcome measure (p>0.05). These findings suggest that a single session of whole-body vibration combined with blood flow restriction does not significantly affect serum sclerostin or bone turnover biomarkers.

FC 133HEMODIAFILTRATION IS ASSOCIATED WITH REDUCED INFLAMMATION AND INCREASED BONE TURNOVER COMPARED TO CONVENTIONAL HEMODIALYSIS IN CHILDREN - THE HDF, HEART AND HEIGHT (3H) STUDY

Background and Aims Children on dialysis have a high burden of bone related comorbidities and fractures. We report a post-hoc analysis of the HDF-Hearts-Height study to determine the prevalence and risk factors for mineral bone disease in children on hemodiafiltration (HDF) and conventional hemodialysis (HD). Method 144 children were included in baseline cross-sectional analysis, of which 103 (61 HD, 42 HDF) completed 12-month follow-up. Biomarkers of bone formation and resorption, inflammatory markers, fibroblast growth factor-23 (FGF23) and klotho were measured. Results Inflammatory markers interleukin-6 [IL-6], tumor necrosis factor-alfa [TNF-α], and high-sensitivity CRP [hsCRP] were lower in the HDF compared to HD cohorts at baseline and 12 months (p&lt;0.001). Concentrations of bone formation (bone-specific alkaline phosphatase, BAP) and resorption (tartrate-resistant acid phosphatase 5b [TRAP5b]) markers were comparable between cohorts at baseline, but after 12-months the BAP/TRAP5b ratio increased in HDF (p=0.004) and was unchanged in HD (p=0.44). On adjusted analysis the BAP/TRAP5b ratio was 2.66-fold lower (95%CI -3.91, -1.41; p&lt;0.0001) in HD compared to HDF. FGF23 was comparable between groups at baseline (p=0.52) but increased in HD (p&lt;0.0001) and remained static in HDF (p=0.34) at 12-months. Klotho levels were similar between groups and unchanged during follow-up. The FGF23/klotho ratio was 3.86-fold higher (95% CI 2.15, 6.93; p&lt;0.0001) in HD compared to HDF. Conclusion We conclude that children on HDF have increased bone turnover, an attenuated inflammatory profile and lower FGF23/klotho ratios compared to those on HD. Long-term studies are required to determine the effect, if any, of an improved bone biomarker profile on fracture risk and growth.

MO807CORRELATIONS BETWEEN THE INFLAMMATORY AND THE BIOCHEMICAL BONE PROFILE OF PATIENTS ON HEMODIALYSIS

Background and Aims End stage kidney disease (ESKD) is associated with a malnutrition-inflammation complex that results in several endocrine, musculoskeletal, and metabolic abnormalities. Despite the known resultant derangements from this process, few studies have evaluated the associations between inflammation and skeletal status in ESKD patients. Our goal is to evaluate correlations between inflammatory and biochemical bone profile within and between dialysis patients and a healthy cohort. Method This analysis is a cross-sectional evaluation of a cohort of 40 dialysis patients and 20 healthy controls. Results Significant differences were found between the dialysis and healthy cohort in biochemical bone profile, inflammatory markers and adipokine levels. Dialysis patients with low vs. high PTH (cutoff 50 pg/mL) had differences in bone turnover markers but no differences in inflammatory or adipokine levels (Table 1). More specifically, bone-specific alkaline phosphatase (BSAP), osteocalcin (OCN) and osteoprotegerin (OPG) were positively correlated with insulin-like growth factors but this correlation was not present after adjustment for parathyroid hormone (PTH) levels. C-terminal cross-linking telopeptide (CTX) positively correlated with IGF1 (p-value 0.02, 95% CI (0.14-1.69)) and with IGFBP3 (p-value 0.007 and 95% CI (0.31- 1.84)) after multivariate adjustment for PTH, albumin and sex. Adiponectin positively correlated with IGFBP3 and this remained significant after adjustment for PTH, albumin and sex (p=0.02). IL6, IL8 and TNF did not correlate with bone turnover markers or with adipokine levels after multivariate adjustments. Conclusion In this cross-sectional study, significant differences were found between the dialysis and healthy cohort in biochemical bone profile, inflammatory markers and adipokine levels. In the dialysis cohort, inflammatory markers did not correlate with bone turnover markers or with adipokine levels in dialysis patients. Dialysis patients with high vs. low PTH (cutoff 50 pg/mL) had higher levels of bone formation and bone resorption markers. Inflammatory and adipokine levels did not differ between those with high vs. low PTH.