Low Serum Parathyroid Hormone Levels Research Articles

Early postoperative PTH level following total thyroidectomy as a predictor of hypocalcemia: a single center-based study in Bangladesh

Background: Assessment of parathyroid hormone (PTH) following thyroid surgery assists in the prediction of hypocalcemia and permits early intervention and therapy with oral calcium and/or vitamin D supplements.
 Methods: This retrospective analysis comprised 141 individuals who had undergone a total or completion thyroidectomy over the previous four years. The blood PTH level was measured 3 hours after surgery to determine its change and to predict hypocalcemia.
 Results: Patients were predominately female (75.2%), and the mean age was 48.73 ± 13.44 years. The main surgical procedure was total thyroidectomy (80.14%), and the main cause for surgery was a multinodular goiter (34.04%). A comparable number of patients with each type of thyroid disease (multinodular goiter, papillary thyroid cancer, thyroiditis, Graves’ disease or toxic multinodular goiter were enrolled. Three hours after surgery 93 patients (65.95%) had serum PTH levels of >10 pg/ml (mean 28.06) and 90 patients (68.38%) had normal serum calcium (mean 8.66). Most of these 93 patients (65.95%) didn't require postoperative supplementation, whereas 48 patients (34.05 %) with serum PTH levels less than 10 pg/ml required some form of supplementation; 39 (27.65 %) required both oral calcium and vitamin D supplements, and 9 (6.4 %) required only oral vitamin D supplementation. There was a significant correlation between the 3-h postoperative PTH level and hypocalcemia (P-value 0.000). The type of pathology had no significant association with low serum PTH level after surgery (P-value 0.166).
 Conclusion: Asymptotic individuals with PTH levels less than 10 pg/ml, who are regarded as being in the high-risk category, can start taking calcium and/or vitamin D supplements early if their PTH levels are measured at 3 hours following complete thyroidectomy. To predict hypocalcemia, more research is required to compare the outcome of early serum PTH level with the day one serum PTH level following complete thyroidectomy.
 Central Medical College Journal Vol 6 No 2 Jauly 2022 Page: 82-89

Relationship between serum parathyroid hormone levels and abdominal aortic calcification in patients starting hemodialysis who have never taken calcium tablets, calcitriol, or vitamin D analogs

Background Vascular calcification (VC) and secondary hyperparathyroidism (SHPT) are important causes of the high incidence of cardiovascular events in chronic kidney disease (CKD) patients. The relationship between parathyroid hormone (PTH) and VC is very complex. The aim of this study was to determine the correlation between PTH levels and abdominal aortic calcification (AAC) in patients starting hemodialysis who had not received calcium tablets, calcium-containing phosphorus binders, calcitriol, or vitamin D analogs. Methods Seventy-one patients were included. Latero-lateral X-ray lumbar radiography, serum intact PTH (iPTH) levels, and predialysis biochemical parameters were obtained. The degree of AAC was evaluated according to the methods described previously by Kauppila et al. Results We found that there was a strong negative correlation between serum PTH and AAC (Spearman’s rho −0.76, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that low serum PTH level could predict the presence and extent of AAC (area under the curve values were 0.9013 [p < 0.0001] and 0.780 [p = 0.0041], respectively). Conclusions Our results indicate that serum PTH level is significantly negatively correlated with AAC within a certain concentration range in patients starting hemodialysis who had not received calcium tablets, calcium-containing phosphorus binders, calcitriol, or vitamin D analogs.

Protective strategy of parathyroid glands during thyroid lobectomy: A retrospective cohort and case-control study.

Parathyroid protection during thyroid lobectomy was not illustrated previously. Aim of this study was to find out the influence of parathyroid glands in situ preservation and autotransplantation on postoperative parathyroid function in thyroid lobectomy.Consecutive patients who underwent primary thyroid lobectomy with unilateral central neck dissection for papillary thyroid carcinoma in our center were included retrospectively. Postoperative hypoparathyroidism was defined as low parathyroid hormone (PTH) levels (<1.6 pmol/L) and keeping over 6 months was defined as permanent. Patients were divided into 3 groups: all identified parathyroid glands preserved in situ (preservation group); at least one parathyroid gland autotransplanted without accidental resection (autotransplantation group); at least one parathyroid gland accidental resected (resection group).A total of 425 patients were included. No permanent hypoparathyroidism was reported, and the rates of transient hypoparathyroidism were similar among all groups. Significantly lower serum PTH levels were found in autotransplantation group versus preservation group at postoperative 1-day (3.77 ± 1.61 vs 4.72 ± 2.31, P < .001). Transient hypoparathyroidism was significantly associated with reduced intraoperative carbon nanoparticles utilization (57.1% vs 77.4%, P = .039).Thyroid lobectomy was a safe surgical method for parathyroid protection no matter the practice to ipsilateral parathyroid glands. However, preservation of all parathyroid glands was still recommended considering relatively stable PTH levels.

The role of early postoperative parathyroid hormone level after total thyroidectomy in prediction of hypocalcemia

BackgroundEstimation of parathyroid hormone (PTH) after thyroid surgery helps to predict the development of hypocalcemia and allows early intervention and management with oral calcium and/or vitamin D supplementation in the postoperative period. Patients and methodsThis retrospective study included 57 patients who underwent total or completion thyroidectomy within 4 years. Measurement of serum PTH level was done 3 h after surgery for its change and prediction of hypocalcemia. ResultsThe mean age was 42.11 years, females constituted 46 patients (80.7%), the main surgical procedure was total thyroidectomy in 51 patients (89.5%), and the main cause for surgery was multinodular goiter in 33 patients (57.8%). Three hours after surgery 47 patients (82.5%) had serum PTH levels of >10 pg/ml (mean 28.06) and 44 patients (77.2%) had normal serum calcium (mean 8.66). Most of these 47 patients (82.46%) didn't require postoperative supplementation, while from other 10 patients (17.5%) with serum PTH level of <10 pg/ml, 7 patients (12.28%) required both oral calcium and vitamin D, and 3 patients (5.26%) required only oral vitamin D.There was a significant correlation between the 3-h postoperative PTH level and hypocalcemia (P-value 0.000). The type of pathology had no significant association with lowserum PTH level after surgery (P-value 0.166). ConclusionPTH measurements at 3 h after total thyroidectomy is an accurate predictor for the development of hypocalcemia and allows starting early calcium and/or vitamin D supplements for the asymptotic patients with PTH level of less than 10 pg/ml, which is considered a high-risk group. Also it facilitates a safe and early (2nd t day post operative) discharge of those patients with serum PTH levels greater than 10 pg/ml without any supplements.Further studies are needed to compare the result of early serum PTH level with the day one serum PTH level after total thyroidectomy to predict hypocalcemia.

Aberrant serum parathyroid hormone, calcium, and phosphorus as risk factors for peritonitis in peritoneal dialysis patients

Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.

Normal parathyroid hormone and non-proliferative diabetic retinopathy in patients with type2 diabetes.

Aims/IntroductionTo investigate the associations between parathyroid hormone (PTH) and non‐proliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes mellitus.Materials and MethodsData were collected from 2,322 patients with type 2 diabetes mellitus in hospital between 2017 and 2019. The odds ratio (OR) and the corresponding 95% confidence interval related to the quartiles of PTH were obtained by logistic regression analysis after adjusting the potential confounding variation.ResultsThe patients were stratified into quartiles (Q1–Q4) based on the PTH levels, with the cut‐off limits of ≤23.74, 23.74–29.47, 29.47–37.30 and >37.30 pg/mL in men, and ≤24.47, 24.47–31.22, 31.22–39.49 and >39.49 pg/mL in women. The first quartile (Q1) represents the lowest quartile and the fourth quartile (Q4) is the highest. According to the quartiles (Q1–Q4), the prevalence rate of NPDR in patients showed a significantly decreasing trend (37.9%, 36.3%, 34.0% vs 24.0% in men; 43.2%, 40.5%, 31.1% vs 26.2% in women, both P < 0.05). Independent of age, diabetes duration and other metabolic factors, multivariate logistic regression showed that participants in Q4 had a lower OR of NPDR than those in Q1 (OR 0.443, 95% confidence interval 0.300–0.654, P < 0.001 for men; OR 0.428, 95% confidence interval 0.283–0.646, P < 0.001 for women).ConclusionsLow serum PTH levels were significantly associated with complications of NPDR in inpatients. Its causality remains to be further studied.

Changes in Volumetric Bone Mineral Density Over 12 Months After a Tibial Bone Stress Injury Diagnosis: Implications for Return to Sports and Military Duty

Background: Bone stress injuries (BSIs) occur in up to 20% of runners and military personnel. Typically, after a period of unloading and gradual return to weightbearing activities, athletes return to unrestricted sports participation or military duty approximately 4 to 14 weeks after a BSI diagnosis, depending on the injury location and severity. However, the time course of the recovery of the bone’s mechanical competence is not well-characterized, and reinjury rates are high. Purpose: To assess the bone microarchitecture and volumetric bone mineral density (vBMD) over 12 months after a tibial BSI diagnosis. Study Design: Case-control study; Level of evidence, 3. Methods: We enrolled 30 female athletes from the local community (aged 18-35 years) with a tibial BSI (grade ≥2 of 4 on magnetic resonance imaging) for this prospective observational study. Participants completed a baseline visit within 3 weeks of the diagnosis. At baseline and 6, 12, 24, and 52 weeks after the BSI diagnosis, we collected high-resolution peripheral quantitative computed tomography scans of the ultradistal tibia (4% of tibial length) of the injured and uninjured legs as well as pain and physical activity assessment findings. Results: From baseline to 12 weeks after the diagnosis, total, trabecular, and cortical vBMD declined by 0.58% to 0.94% (P < .05 for all) in the injured leg. Total and trabecular vBMD also declined by 0.61% and 0.67%, respectively, in the uninjured leg (P < .05 for both). At 24 weeks, mean values for all bone parameters were nearly equivalent to baseline values, and by 52 weeks, several mean values had surpassed baseline values. Of the 30 participants, 10 incurred a subsequent BSI during the course of the study, and 1 of these 10 incurred 2 subsequent BSIs. Participants who suffered an additional BSI were younger and had a later age of menarche, a greater incidence of previous fractures, and lower serum parathyroid hormone levels (P < .05 for all). Conclusion: Bone density declined in both the injured and the uninjured legs and, on average, did not return to baseline for 3 to 6 months after a tibial BSI diagnosis. The observed time to the recovery of baseline vBMD, coupled with the high rate of recurrent BSIs, suggests that improved return-to-sports and military duty guidelines may be in order.

Лечение минерально-костных нарушений при хронической болезни почек

Mineral-bone disorders (MBD) in chronic kidney disease (CKD) manifest by hyperphosphatemia, vitamin D deficiency, overproduction of fibroblast growth factor-23, and secondary hyperparathyroidism. CKD-MBD also results in bone resorp-tion and ectopic calcification that is associated with an increased risk of cardiovascular events and mortality. Diet is the initial and obligatory approach to treatment for CKD-MBD. Sevelamer is frequently used for correction of hyperphosphatemia in patients with renal failure who present with calcification of arteries, adynamic bone disease and/or stably low serum parathyroid hormone levels. Calcimimetics, that is, cinacalcet and evocalcet, are widely used in hemodialysis patients who do not respond to treatment with vitamin D.

Hemodialysis patients with low serum parathyroid hormone levels have a poorer prognosis than those with secondary hyperparathyroidism.

Background:Low serum parathyroid hormone (PTH) level and secondary hyperparathyroidism (SHPT) are very common in hemodialysis patients. However, the outcomes of patients with low PTH level or SHPT have not been carefully compared. Therefore, in the present study, we compared the outcomes of hemodialysis patients with low PTH level or SHPT.Methods:This was a multi-center, prospective, cohort study of 647 patients. The patients were recruited between 1 September 2016 and 1 January 2017 and followed until 31 December 2018. The participants were allocated to a low PTH group [serum intact PTH (iPTH) concentration < 60 pg/ml] and an SHPT group (iPTH ⩾ 600 pg/ml) according to their mean iPTH concentration across the entire observation period, and the outcomes were compared between these groups. The primary outcome was a composite outcome, which comprised all-cause mortality, non-fatal acute myocardial infarction, non-fatal acute stroke, and acute heart failure.Results:A total of 197 hemodialysis patients were allocated to the two groups: 87 with low PTH level and 110 with SHPT; 450 patients with time-averaged iPTH concentrations of 60–600 pg/ml were excluded. Kaplan–Meier analysis of the composite endpoint revealed a significant difference between participants with low PTH level and those with SHPT (p = 0.002). Cox multiple regression showed that participants with low PTH level had a higher incidence of the composite endpoint than those with SHPT (relative risk: 1.337, 95% confidence interval: 1.059–1.688).Conclusion:Hemodialysis patients with low PTH level had a higher incidence of mortality and non-fatal cardiovascular events than those with SHPT, irrespective of whether the participants were age-matched.

Electrolyte disorders in a young female following short-term omeprazole therapy

A 29 years old female presented to us in the metabolic clinic of the University of Port Harcourt Teaching Hospital (UPTH) on account of a week history of easy fatigability, weakness, and lower extremity muscle cramps associated with numbness and tingling sensation in the peri-oral area, fingers and toes. Two weeks prior to the onset of her presenting symptoms, she had visited a local pharmaceutical shop on account of a distressing epigastric discomfort and was subsequently placed on daily oral omeprazole 20mg daily for a month by a pharmacist. She had been on the omeprazole medication for two weeks before her present symptoms manifested. Her past medical history was not suggestive of hypoparathyroidism nor pancreatitis. She was married with three children and has an uneventful family, social and obstetric histories. On examination, she was a healthy well-oriented young female with positive Trousseau’s, Chvostek’s and epigastric tenderness signs. Further Laboratory evaluation revealed she had low plasma magnesium, low plasma albumin-corrected calcium, and low serum parathyroid hormone levels, while other laboratory parameters were essentially normal. A diagnosis of omeprazole-induced electrolyte disorders (hypomagnesaemia and hypocalcaemia) associated with hypoparathyroidism was made following the review of her clinical examination and laboratory findings. She was subsequently managed with oral magnesium supplements following the withdrawal of the omeprazole medication (replaced with oral ranitidine), monitored weekly, and full recovery was achieved after three weeks.

Vertebral fractures and bone mineral density in patients with idiopathic hypoparathyroidism on long term follow-up

Bone mineral density (BMD) is increased in idiopathic hypoparathyroidism (IH). Parathyroid hormone (PTH) deficiency, hypocalcemic seizures, and anticonvulsants could compromise skeletal health in IH. We assessed vertebral fractures (VFs) and related factors in IH and change in BMD during follow-up. VFs were assessed by morphometry. BMD was assessed by dual-energy X-ray absorptiometery at the lumbar spine, hip, and forearm. Change in BMD was assessed in a subset after a 10-year follow-up. The endocrine clinic of All India Institute of Medical Sciences, New Delhi, India. Included were 104 patients with IH and 64 healthy controls. Hypocalcemia, hyperphosphatemia, normal kidney function, and low serum PTH levels were used to diagnose IH. VFs were seen in 18.3% of patients with IH and 4.7% of controls (odds ratio, 4.54; 95% confidence interval, 1.28 to 16.04). Use of anticonvulsants and menopause were significantly associated (P < 0.05) with VF. Mean BMD at lumbar spine and hip were higher by 21.4% and 8.6%, respectively, in IH than in controls (P < 0.001), respectively. BMD significantly increased during follow-up at all sites. Change in BMD correlated with maintenance of the serum calcium/phosphorus ratio during follow-up. Despite increased BMD, prevalence of vertebral-fractures is greater in patients with IH, especially in postmenopausal women and those on anticonvulsant therapy.

Negative association between serum parathyroid hormone levels and urinary perchlorate, nitrate, and thiocyanate concentrations in U.S. adults: the National Health and Nutrition Examination Survey 2005-2006.

ObjectivesPerchlorate, nitrate, and thiocyanate are well-known inhibitors of the sodium-iodide symporter and may disrupt thyroid function. This exploratory study investigated the association among urinary perchlorate, nitrate, and thiocyanate concentrations and parathyroid hormone (PTH) levels in the general U.S. population.MethodsWe analyzed data on 4265 adults (aged 20 years and older) from the National Health and Nutrition Examination Survey in 2005 through 2006 to evaluate the relationship among urinary perchlorate, nitrate, and thiocyanate concentration and PTH levels and the presence of hyperparathyroidism cross-sectionally.ResultsThe geometric means and 95% confidence interval (95% CI) concentrations of urinary perchlorate, nitrate, and thiocyanate were 3.38 (3.15–3.62), 40363 (37512–43431), and 1129 (1029–1239) ng/mL, respectively. After adjusting for confounding variables and sample weights, creatinine-corrected urinary perchlorate was negatively associated with serum PTH levels in women (P = 0.001), and creatinine-corrected urinary nitrate and thiocyanate were negatively associated with serum PTH levels in both sex groups (P = 0.001 and P<0.001 for men, P = 0.018 and P<0.001 for women, respectively). Similar results were obtained from sensitivity analyses performed for exposure variables unadjusted for creatinine with urinary creatinine added as a separate covariate. There was a negative relationship between hyperparathyroidism and urinary nitrate and thiocyanate [odds ratio (95% CI) = 0.77 (0.60–0.98) and 0.69 (0.61–0.79), respectively].ConclusionsA higher urinary concentration of perchlorate, nitrate, and thiocyanate is associated with lower serum PTH levels. Future studies are needed to determine the pathophysiological background of the observation.

High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients.

Excess parathyroid hormone (PTH), known as primary hyperparathyroidism (pHPT), results in hypercalcemia and bone loss. Recent studies have shown that PTH is associated with the occurrence of hypertension in Western countries; however, controversy remains regarding high serum levels of PTH and calcium as risk factors for hypertension in Japanese patients. We retrospectively enrolled 114 consecutive Japanese patients who visited our hospital for examination and treatment of hypercalcemia and/or hypertension with serum calcium levels ≥ 9.8 mg/dL. To estimate the prevalence of hypertension, the patients were categorized according to calcium levels into hypercalcemic (10.2-13.4 mg/dL) and normocalcemic (9.8-10.1 mg/dL) groups, which were further categorized into high PTH (50-440 pg/mL) and low PTH (8-49 pg/mL) groups. The prevalence of hypertension was higher in patients with hypercalcemia than in patients with normocalcemia in both the high and low PTH groups. The prevalence of hypertension was higher in patients with high serum PTH levels than in patients with low serum PTH levels in both the hypercalcemic and normocalcemic groups. Logistic multiple regression analysis determined that serum calcium (P < 0.05) and PTH (P < 0.01) levels were positive contributors to hypertension. In conclusion, high serum levels of PTH and calcium are risk factors for hypertension in Japanese patients.

Cinacalcet in Patients with Chronic Kidney Disease: A Cumulative Meta-Analysis of Randomized Controlled Trials

Calcimimetic agents lower serum parathyroid hormone levels in people with chronic kidney disease (CKD), but treatment effects on patient-relevant outcomes are uncertain. We conducted a systematic review and meta-analysis to summarize the benefits and harms of calcimimetic therapy in adults with CKD and used cumulative meta-analysis to identify how evidence for calcimimetic treatment has developed in this clinical setting. Cochrane and Embase databases (through February 7, 2013) were electronically searched to identify randomized trials evaluating effects of calcimimetic therapy on mortality and adverse events in adults with CKD. Two independent reviewers identified trials, extracted data, and assessed risk of bias. Eighteen trials comprising 7,446 participants compared cinacalcet plus conventional therapy with placebo or no treatment plus conventional therapy in adults with CKD. In moderate- to high-quality evidence (based on Grading of Recommendations Assessment, Development, and Evaluation criteria) in adults with CKD stage 5D (dialysis), cinacalcet had little or no effect on all-cause mortality (relative risk, 0.97 [95% confidence interval, 0.89-1.05]), had imprecise effect on cardiovascular mortality (0.67 [0.16-2.87]), and prevented parathyroidectomy (0.49 [0.40-0.59]) and hypercalcemia (0.23 [0.05-0.97]), but increased hypocalcemia (6.98 [5.10-9.53]), nausea (2.02 [1.45-2.81]), and vomiting (1.97 [1.73-2.24]). Data for clinical outcomes were sparse in adults with CKD stages 3-5. On average, treating 1,000 people with CKD stage 5D for 1 y had no effect on survival and prevented about three patients from experiencing parathyroidectomy, whilst 60 experienced hypocalcemia and 150 experienced nausea. Analyses were limited by insufficient data in CKD stages 3-5 and kidney transplant recipients. Cinacalcet reduces the need for parathyroidectomy in patients with CKD stage 5D, but does not appear to improve all-cause or cardiovascular mortality. Additional trials in CKD stage 5D are unlikely to change our confidence in the treatment effects of cinacalcet in this population.

Hypercalcemia Associated with Eosinophilic Myocarditis in a Patient Undergoing Maintenance Hemodialysis

A 77-year-old man previously treated with maintenance hemodialysis was admitted due to appetite loss, nausea and shortness of breath. He showed progressive heart failure and eosinophilia without any basal disorders and was diagnosed with idiopathic hypereosinophilic syndrome (HES) accompanied by eosinophilic myocarditis. Laboratory data revealed hypercalcemia, a low serum parathyroid hormone level and a high 1,25(OH)(2)D concentration in spite of renal failure and no causal medications. Steroid therapy resulted in the patient's rapid recovery from heart failure, hypereosinophilia and hypercalcemia. Since the serum 1,25(OH)(2)D level promptly and markedly decreased, the hypercalcemia complicated with HES was most likely caused by extrarenal production of 1,25(OH)(2)D.

New American Thyroid Association and American Association of Clinical Endocrinologists Guidelines for Thyrotoxicosis and Other Forms of Hyperthyroidism: Significant Progress for the Clinician and a Guide to Future Research

New American Thyroid Association and American Association of Clinical Endocrinologists Guidelines for Thyrotoxicosis and Other Forms of Hyperthyroidism: Significant Progress for the Clinician and a Guide to Future Research

Effect of Alfacalcidol on Anemia in Renal Failure Patients

Background: Anemia is a major feature of chronic kidney disease (CKD). Additionally, secondary hyperparathyroidism (SHPT) has been associated with anemia in uremic patients. Administration of active vitamin D metabolites like alfacalcidol is established for PTH suppression and may also play a role in hematopoiesis. Aim:To investigate the effect of alfacalcidol on anemia and SHPT with end stage renal failure patients underwent hemodialysis. Subjects and Methods: In the present study 17 anemic patients over 15years, with serum level of PTH greater than 500pg/ml. The study was carried out by means of data collection and analysis of serum parathyroid hormone (PTH) and hemoglobin (Hb) levels in these patients. Results: Low serum PTH levels were detected in uremic patients treated with alfacalcidol. Also, in these patients, Hb levels increased. Serum PTH and Hb levels were inversely correlated. Conclusions: High-dose alfacalcidol can decrease serum PTH levels and elevate Hb level in uremic patients showing considerable resistance to Epoetin.

Vitamin K2 Alters Bone Metabolism Markers in Hemodialysis Patients with a Low Serum Parathyroid Hormone Level

Background: A low level of intact parathyroid hormone (PTH) is an indicator of adynamic bone disease in hemodialysis patients, and is associated with a significant increase of all-cause mortality. Thus, effective treatment for adynamic bone disease is required. We previously investigated the effect of vitamin K₂ on adynamic bone disease. In this study, we assessed the efficacy of oral vitamin K₂ in a controlled trial. Methods: Forty hemodialysis patients with low intact PTH levels (<100 pg/ml) were randomly divided into two groups, which were a vitamin K₂ group receiving oral menatetrenone (45 mg/day) for 1 year and a control group without vitamin K₂. Venous blood samples were collected at baseline and during the study for measurement of bone metabolism parameters. Results: Thirty-three patients completed follow-up. There was a significant increase of the serum intact osteocalcin level after 1 month of vitamin K₂ administration. Serum levels of intact PTH, bone alkaline phosphatase, and cross-linked N-terminal telopeptide of type I collagen increased significantly after 12 months in the vitamin K₂ group. The serum osteoprotegerin level was decreased after 12 months in the vitamin K₂ group, but the change was not significant. Conclusion: Vitamin K₂ therapy improves bone remodeling in hemodialysis patients with a low intact PTH level.

Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1α-hydroxylase

Changes in the expression of klotho, a beta-glucuronidase, contribute to the development of features that resemble those of premature aging, as well as chronic renal failure. Klotho knockout mice have increased expression of the sodium/phosphate cotransporter (NaPi2a) and 1alpha-hydroxylase in their kidneys, along with increased serum levels of phosphate and 1,25-dihydroxyvitamin D. These changes are associated with widespread soft-tissue calcifications, generalized tissue atrophy, and a shorter lifespan in the knockout mice. To determine the role of the increased vitamin D activities in klotho knockout animals, we generated klotho and 1alpha-hydroxylase double-knockout mice. These double mutants regained body weight and developed hypophosphatemia with a complete elimination of the soft-tissue and vascular calcifications that were routinely found in klotho knockout mice. The markedly increased serum fibroblast growth factor 23 and the abnormally low serum parathyroid hormone levels, typical of klotho knockout mice, were significantly reversed in the double-knockout animals. These in vivo studies suggest that vitamin D has a pathologic role in regulating abnormal mineral ion metabolism and soft-tissue anomalies of klotho-deficient mice.

Fracture Risk after Parathyroidectomy among Chronic Hemodialysis Patients

The impact of parathyroidectomy (PTX) on the long-term risks for hip and other fractures is unknown. Uncontrolled case series have reported an increase in bone mineral density after PTX. However, very low serum parathyroid hormone levels have been associated with decreased bone mineral density, adynamic bone disease, and fractures. This study compared long-term fracture rates among hemodialysis patients who underwent PTX with a matched control group. Data were obtained from the US Renal Data System. Patients who underwent a first PTX while receiving hemodialysis were matched with up to three control patients by age, race, gender, year of dialysis initiation, primary cause of renal failure, and the dosage of intravenous vitamin D used before PTX. Patients with a history of fracture or renal transplantation were excluded. Study outcomes were incident hip, vertebral, and distal radius-wrist fractures identified using hospitalization codes. Incident hip fracture rates in the PTX and matched control groups were 6.0 and 9.3 fractures per 1000 person-years, respectively. After adjustment, PTX was associated with a significant 32% lower risk for hip fracture (95% confidence interval 0.54 to 0.86; P = 0.001) and a 31% lower risk for any analyzed fracture (95% confidence interval 0.57 to 0.83; P < 0.001) compared with matched control subjects. Fracture risks were lower among hemodialysis patients who underwent PTX compared with matched control subjects. Surgical amelioration of secondary hyperparathyroidism may outweigh the risk of parathyroid hormone oversuppression in terms of bone health.