Increased Parathyroid Hormone Research Articles

Hormonal and Mineral Imbalance Effect on Bone Resorption in Predialysis Iraqi Patients with Chronic Kidney Disease

Introduction: Chronic kidney disease mineral bone disorder is a metabolic bone disease present in almost all uremic patients. The aim of this research to indicate the stage of chronic kidney disease (CKD) that affect the bone metabolism that leading to the mineral and hormonal imbalance by studying the relationship among osteocalcin , glomerular filtration rate (GFR), parathyroid hormone, calcium and phosphorus levels in the blood. Method: The study included 52 patients with predialysis chronic kidney disease stage 3-5 and 40 apparently healthy relatives accompanying the patients. Glomerular filtration rate (GFR) was calculated for each patient. Renal function tests, including serum levels of urea, creatinine, a biochemical marker of bone metabolism: osteocalcin (OSN), calcium, phosphorus, and parathyroid hormone (PTH), were measured for each participant. Results: Serum urea and creatinine levels were significantly higher in CKD patients Than that of apparently healthy control. There is significantly higher serum parathyroid hormone, serum phosphorus, serum osteocalcin (P<0.01, P<0.01, P<0.01 respectively) in CKD patients than that of the healthy control group. While low serum calcium level in CKD patients as compared to the corresponding group (P<0.01). Conclusion: Hyperphosphatemia and hypocalcemia in the end stage of predialysis CKD patients lead to increase parathyroid hormone secretion, which causes high bone turnover characterized by significantly high serum osteocalcin in these patients. Parathyroid hormone and osteocalcin were used as a biomarker for the development of bone and mineral disorders in predialysis CKD patients.

Serum PTH is not a good marker for defining a threshold for vitamin D deficiency.

ObjectiveIn addition to its skeletal effects, vitamin D may also be important for health in general. It is uncertain what level of serum 25-hydroxyvitamin D (25(OH)D), marker of vitamin D status, is sufficient for these effects. With decreasing serum 25(OH)D levels there is an increase in serum PTH. The point at which this occurs has been considered as a threshold for vitamin D sufficiency. The thresholds found have varied widely and have mainly been based on observational studies. However, to truly establish a threshold for vitamin D effects, this has to be based on randomized controlled trials (RCTs).MethodsThe study included 2803 subjects from a general health survey, the Tromsø study, and pooled individual person data from five vitamin D intervention studies (n = 1544). Serum parathyroid hormone (PTH) and change in PTH after vitamin D supplementation were related to serum 25(OH)D levels in steps of 25 nmol/L (<24, 25–49, 50–74, 75–99, and >99 nmol/L).ResultsIn the Tromsø study, in the females there was a gradual decrease in serum PTH with increasing serum 25(OH)D with no apparent plateau, whereas in the males the decrease in PTH in subjects with serum 25(OH)D >74 nmol/l was marginal. In pooled RCTs, there was a significant reduction in serum PTH by vitamin D supplementation regardless of baseline serum 25(OH)D level.ConclusionsThe use of the serum PTH–25(OH)D relation from observational studies to determine a threshold for vitamin D sufficiency is highly questionable.

Primary Hyperparathyroidism in Sickle Cell Disease: An Unknown Complication of the Disease in Adulthood.

Primary hyperparathyroidism (pHPT) is the third most common endocrine disorder and usually affects patients between 60 and 70 years of age. To our knowledge, this condition has never been studied in young patients with sickle cell disease (SCD). Our objective was to describe the clinical and biological characteristics of pHPT in adult patients with SCD and its management. We conducted a retrospective study that included SCD patients who were diagnosed with pHPT in four SCD referral centers. pHPT was defined by the presence of elevated serum calcium levels with inappropriate normal or increased parathyroid hormone (PTH) serum levels or histopathological evidence of parathyroid adenoma or hyperplasia. Patients with severe renal impairment (GFR <30 mL/min) were excluded. Twenty-eight patients (18 women, 64%; 22 homozygous genotype, 79%) were included. The median age at pHPT diagnosis was 41 years (interquartile range –IQR- 31.5–49.5). The median serum calcium and PTH concentration were, respectively, 2.62 mmol/L (IQR 2.60–2.78) and 105 pg/mL (IQR 69–137). Bone mineral density (BMD) revealed very low BMD (≤−2.5 SD) in 44% of patients explored (vs. 12.5% among 32 SCD patients matched for SCD genotype, sex, age, and BMI, p = 0.03). Fourteen patients (50%) received surgical treatment, which was successful in all cases, but four of these patients (29%) presented with pHPT recurrence after a median time of 6.5 years. Three of these patients underwent a second cervical surgery that confirmed the presence of a new parathyroid adenoma. These results suggest that SCD is a condition associated with pHPT in young subjects. SCD patients with pHPT have a high risk of very low BMD. A diagnosis of pHPT should be suspected in the presence of mild hypercalcemia or low BMD in SCD patients.

Хондрокальциноз как ранний признак первичного гиперпаратиреоза

Objective: To deeply analyse a case of a patient with calcium pyrophosphate crystal storage disease, where chondrocalcinosis (CC) preceded primary hyperparathyroidism (PHPT). Key Points. The association of CC and hyperparathyroidism is well-known; and CC is recognised as one of the late signs of hyperparathyroidism. We describe a 67-year old patient with PHPT, presenting for a long time only with X-ray CC and chronic arthritis, associated with calcium pyrophosphate deposits. At the same time, he did not have any electrolyte imbalances, had normal serum calcium and parathyroid hormone levels; PHPT was diagnosed after 10 years of follow-up when the patient developed life-threatening hypercalcemia. It can be assumed that, unlike other musculoskeletal signs, CC can be one of the earliest symptoms of hyperparathyroidism. Treating CC as a late sign of hyperparathyroidism is likely to be associated with challenges of early diagnosis (asymptomatic in some patients, low sensitivity of X-ray diagnostics). In order to assess the diagnostic value of CC in hyperparathyroidism, including patients with normal calcium levels, specific tests are essential. Conclusion. Target examination for CC using highly-sensitive methods in patients with minor calcium metabolism disturbances, high/normal parathyroid hormone level or slightly increased parathyroid hormone level and normal calcium can improve the detection frequency of both CC and PHPT and follow-up of such patients. Early PHPT diagnosis (prior to clinical presentation) can help in preventing severe, life-threatening complications. Keywords: chondrocalcinosis, primary hyperparathyroidism, parathyroid hormone, calcium pyrophosphate crystal storage disease, hypercalcemia.

A case report of tetanic crisis from acute severe hypocalcemia secondary to hypovitaminosis D: analysis of risk factors for vitamin D deficiency between 1 and 18 years

Background: Hypocalcemia is one of the most common disorders of metabolism in children. One of the most known causes is hypovitaminosis D, an extremely widespread condition in the world, both in developed and developing countries. Etiology is related to poor exposure to sunlight and inadequate diet, especially in subjects with dark skin or exclusively breastfed or born to mothers with vitamin D deficiency by ethnic and cultural reasons. Case Presentation: We report a case of a teenager from Morocco, who presented a tetanic crisis in the course of influenza B. The laboratory tests showed severe hypocalcemia and low serum vitamin D concentration with increased parathyroid hormone value. The administration of calcium and vitamin D normalized the clinical and laboratory parameters. Conclusions: Adolescents of ethnic groups at risk frequently find themselves in a chronic situation of altered metabolism deriving from vitamin D deficiency. Hence, a simple insult, as influenza B virus, can lead to severe pathological manifestations.

Increased parathyroid hormone is associated with higher fasting glucose in individuals with normocalcemic primary hyperparathyroidism and prediabetes: A pilot study

AimsThis pilot study aimed to evaluate differences in glycemic parameters between patients with prediabetes and normocalcemic primary hyperparathyroidism (NPHPT) and controls with prediabetes and normal parathyroid hormone (PTH) and calcium concentrations. Methods20 patients with NPHPT and prediabetes and 42 age-, gender-, and body mass index-matched controls with prediabetes were included. Glycemic parameters [fasting glucose (fGlu), glycosylated hemoglobin (HbA1c), fasting insulin (fIns)] were evaluated. Homeostasis Model Assessment was used for estimating insulin secretion (HOMA-B) and resistance (HOMA-IR). Participants underwent a 75-g oral glucose tolerance test. ResultsHbA1c (5.9 ± 0.0 vs 5.9 ± 0.0%, p = 0.44), HOMA-IR (3.7 ± 1.2 vs 2.9 ± 0.2, p = 0.48), HOMA-B (117.8 ± 31.8 vs 146.9 ± 22.0%, p = 0.14), fIns (14.0 ± 4.3 vs 12.2 ± 1.1 μIU/ml, p = 0.53) and 2-hour post-load glucose concentrations (157.2 ± 2.2 vs 152.2 ± 2.0 mg/dl, p = 0.07), were nondifferent in the two groups. Higher fGlu levels were evident in the NPHPT, compared to the control group (105.6 ± 2.8 vs 98.2 ± 1.8 mg/dl, p = 0.01). fGlu demonstrated a positive correlation with PTH concentrations (rho = 0.374, p = 0.005). ConclusionsIndividuals with NPHPT and prediabetes present an unfavorable glycemic profile compared to age-matched people with prediabetes, suggesting a direct adverse effect of elevated PTH on glucose homeostasis.

Children and adolescents with obesity have reduced serum bone turnover markers and 25-hydroxyvitamin D but increased parathyroid hormone concentrations - Results derived from new pediatric reference ranges.

We aimed to establish age- and gender-specific reference ranges for concentrations of the bone markers osteocalcin (OC), procollagen type 1N-propeptides (PINP) and carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX-I) as well as for the calciotropic hormones 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) in healthy infants, children and adolescents. In addition, the effect of age, gender, puberty and body mass index (BMI) on bone markers was investigated. 2416 healthy subjects (5714 blood withdrawals), aged 3months to 17years, were included to estimate the age- and gender-dependence of reference ranges. Subsequently, measured values of the biomarkers were transformed to standard deviation scores (SDS) and their associations with age, gender and puberty were analyzed. Bone marker-SDS values of the reference cohort were compared with an obese cohort (n=317 and 489 blood withdrawals) to analyze the effect of BMI. OC, PINP and CTX-I showed a distinct age- and gender-dependence with peak levels at 10 to 11years (girls, Tanner 3) and 13years (boys, Tanner 3-4). Children with obesity had significantly lower SDS levels for OC (-0.44), PINP (-0.27), CTX-I (-0.33), 25(OH)D (-0.43) and higher SDS levels for PTH (+0.44) than the reference cohort. OC, PINP and CTX-I vary with age, gender and pubertal stage. The body weight status has to be considered in the interpretation of pediatric OC, PINP, CTX-I, 25(OH)D and PTH levels. Consequences of childhood obesity on bone health should be carefully investigated in long-term studies.

Failure to Increase Parathyroid Hormone Predicts Hypocalcemia After Neck Surgery for Endocrine Diseases: A Referral Center Experience With High Risk Patients

Failure to Increase Parathyroid Hormone Predicts Hypocalcemia After Neck Surgery for Endocrine Diseases: A Referral Center Experience With High Risk Patients

A patient with extensive cerebral calcification due to pseudohypoparathyroidism: a case report

BackgroundPseudohypoparathyroidism(PHP) is a heterogeneous group of disorders due to impaired activation of c AMP dependant pathways following binding of parathyroid hormone (PTH) to its receptor. In PHP end organ resistance to PTH results in hypocalcaemia, hyperphosphataemia and high PTH levels.Case presentationA 59 year old male presented with a history of progressive impairment of speech and unsteadiness of gait for 1 week and acute onset altered behavior for 1 day and one episode of generalized seizure. His muscle power was grade four according to MRC (medical research council) scale in all limbs and Chovstek’s and Trousseau’s signs were positive. Urgent non contrast computed tomography scan of the brain revealed extensive bilateral cerebral and cerebellar calcifications. A markedly low ionized calcium level of 0.5 mmol/l, an elevated phosphate level of 9.5 mg/dl (reference range: 2.7–4.5 mg/dl) and an elevated intact PTH of 76.3 pg/l were noted. His renal functions were normal. His hypocalcemia was accentuated by the presence of hypomagnesaemia. His 25 hydroxy vitamin D level was only marginally low which could not account for severe hypocalcaemia. A diagnosis of pseudohypoparathyroidism without phenotypic defects, was made due to hypocalcaemia and increased parathyroid hormone levels with cerebral calcifications. The patient was treated initially with parenteral calcium which was later converted to oral calcium supplements. His coexisting Vitamin D deficiency was corrected with 1αcholecalciferol escalating doses. His hypomagnesaemia was corrected with magnesium sulphate parenteral infusions initially and later with oral preparations. With treatment there was a significant clinical and biochemical response.ConclusionPseudohypoparathyroidism can present for the first time in elderly resulting in extensive cerebral calcifications. Identification and early correction of the deficit will result in both symptomatic and biochemical response.

Parathyroid Hormone and Ischemic Cerebrovascular Event.

Increased parathyroid hormone (PTH) level is associated with coronary artery disease, hypertension and left ventricular hypertrophy which are all predisposing factors for the ischemic cerebrovascular event (ICVE). Carotid intima-media thickness (CIMT) and aortic distensibility are the two early, subclinical predictors of atherosclerosis. The relation of PTH with CIMT and aortic distensibility in patients with ICVE has not been previously studied. Our aim was to study the relationship of PTH levels with aortic distensibility and CIMT in patients with ICVE. Sixty-four ICVE patients and 50 control group were enrolled in the study. PTH levels, aortic distensibility and CIMT were measured in all individuals. PTH levels were significantly higher in ICVE patients than in the controls (60.1±21.6 vs. 52.3±6.2 pg/ml) (p=0. 008). PTH levels were found to be inversely correlated with aortic distensibility (r= -0. 420, p=0.001) and positively correlated with CIMT (r:0, 285, p=0,002). The present study shows that PTH levels are increased in patients with acute ischemic cerebrovascular event compared to the control group. It also demonstrates that PTH levels are inversely related to aortic distensibility of ascending aorta and positively associated with CIMT.

Derivation of a cost-saving screening strategy for asymptomatic primary hyperparathyroidism

BackgroundOur study seeks to find a cost-saving screening strategy in a primary care population for diagnosing primary hyperparathyroidism based on peak serum total calcium level, age, and patient sex. MethodsLaboratory data resulting from primary care office visits at our institution between January 2016 through December 2017 to evaluate patients who had at least 1 episode of hypercalcemia (≥10.5 mg/dL). For each serum calcium threshold, we calculated the percentage of patients who were found to have an increased parathyroid hormone level (≥65 pg/mL). We determined whether net cost savings could be achieved by screening hypercalcemic patients given their probability of primary hyperparathyroidism and expected cost savings from fracture risk reduction, given their sex and age. ResultsFrom 155,350 unique patients in the study period, a total of 2,271 had a minimum of 1 hypercalcemic lab value. After exclusion criteria, there were 1,326 patients of whom 27.5% had a parathyroid hormone level checked. Cost savings was established at a screening threshold of 10.5 for all patients until age 66 years for men and 69 years for women. For men aged 67–68 y and women aged 70–71 years, the optimal screening threshold was 10.8 mg/dl. ConclusionCost savings can be achieved by screening hypercalcemic patients with a life expectancy exceeding 16 years, with varying thresholds based on age and sex.

A155 Parathyriod hormone changes after sleeve gastrectomy: a systematic review and meta-analysis

Roux-en-Y gastric bypass (RYGB) adversely affects bone health resulting in low calcium, low vitamin D and increased parathyroid hormone (PTH) due to its malabsorptive mechanism. The evidence is less well described for sleeve gastrectomy (SG). This meta-analysis aimed to identify all studies that collected data on changes in PTH, calcium and 25-hydroxyvitamin D [25(OH)D] after SG.

Update - Calcium Metabolism

A finely balanced control system keeps the extracellular calcium concentration within narrow limits. Disorders of calcium metabolism are often based on altered parathormone levels. Symptoms are not always clear, sometimes they are even missing: the more it is important to know possible associated diseases. The author presents basics, current diagnostics and concrete therapy options. Central hormone for the regulation of the calcium balance is the parathyroid hormone. With decreasing calcium, PTH leads to an increase in extracellular free calcium concentration in three ways. The classic symptoms of pHPT (polyuria, polydipsia, "stone, leg, and stomach pain") are rare now, as the condition is diagnosed much earlier. Treatment of choice in all symptomatic patients with pHPT is surgery. FHH and pHPT are both characterized by hypercalcaemia and increased parathyroid hormone. The differential diagnosis of urinary calcium excretion, which is usually lower in FHH but normal or elevated in pHPT, is crucial. In primary hypoparathyroidism, parathyroid failure interferes with calcium homeostasis at a central location. Consequences are hypocalcaemia, hyperphosphatemia and lack of active vitamin D. Due to increased urinary calcium excretion, patients with ADH are at high risk for kidney stones, nephrocalcinosis and the development of renal insufficiency. Recently, rhPTH 1-84 has been available for the treatment of hypoparathyroidism. However, long-term data is still lacking to provide a safe indication, considering potential effects and side effects.

Mid-Term Outcomes of Primary Hip Replacement in Patients with End-Stage Chronic Renal Disease

Purpose — to evaluate mid-term outcomes of primary hip replacement in patients with end-stage chronic renal disease and to develop an algorithm for selection of surgical tactics and perioperative treatment.Materials and Methods. The authors evaluated outcomes of primary hip replacement in 45 patients receiving renal substitution therapy and 47 patients without chronic renal disease. Patients with end-stage chronic renal disease (CRD) were divided into two groups: group I included 30 (66.6%) patients receiving chronic hemodialysis (CH) and group II included 15 (33.4%) patients after renal transplantation (RT). Group III of 47 (51.1%) patients without any signs of CRD who underwent hip arthroplasty within relevant period of time was established to evaluate the effectiveness of primary hip replacement. Blood serum Ca2+ and P5+ levels as well as levels of parathyroid hormone (PTH) and 1.25-dihydroxyvitamin D were measured to determine the rate of calcium- phosphoric metabolism disturbance. Multi-spiral CT scans of hip joint were performed to identify bone mineral density and the mean Hounsfield (Hu) value was calculated for which the data was obtained from five various points on the proximal femur and acetabulum. Beta-2 microglobulin (B2M) blood test was performed to confirm amyloid bone disease.Results. The authors did not observe statistically significant differences for arthroplasty outcomes in patients of group II and III. Patients receiving long-term hemodialysis demonstrated significantly lower parameters of Harris score and Barthel’s index of social adaptation after hip replacement as compared to groups II and III: patients of group I demonstrated outcomes improvement at 19.55%, in group II — at 13.03%, in group III — at 10.15% as compared to preoperative status. Decrease of 1.25-dihydroxyvitamin D below 20,0 mcg results in resorption of cancellous bone in proximal femur and acetabulum along with myopathy of gluteus muscles. Sharp increase of parathyroid hormone level (over 600 pcg/ml) was accompanied by inhibition of osteoblasts proliferation and differentiation resulting in substantial impairment of mineralization.Conclusion. According to the algorithm suggested by the authors the key parameters that need to be evaluated in preoperative period are parathyroid hormone (PTH) and 1.25-dihydroxyvitamin D. Five-fold increase of PTH (600 pcg/ml) demands parathyroidectomy as the first stage of treatment to decrease risk of early aseptic loosening of hip prosthesis and development of periprosthetic fracture.

99mTc-MIBI SPECT/CT imaging contribution in the diagnosis of patients with hyperparathyroidism

Introduction: Hyperparathyroidism is presented with increased parathyroid hormone (PTH) secretion due to hyperfunctioning of one or more of the four parathyroid glands. Primary hyperparathyroidism (p-HPT) can be due to parathyroid adenoma, hyperplasia or carcinoma of the parathyroid gland. Secondary hyperparathyroidism (s-HPT) is usually a response to hypocalcaemia and consecutive hyperplasia of the glands. Our aim was to compare the efficacy of 99mTcmethoxyisobutylisonitrile (MIBI) SPECT/CT in identification of the location of the lesion(s) in cases of HPT by comparing these results with the findings of ultrasound (US) and planar scintigraphy. Methods: Forty one consecutive patients (54±17 age, 12 males and 29 females) with primary or secondary hyperparathyroidism were included. All patients were examined by US and afterwards patients underwent conventional double-phase 99mTc-MIBI scintigraphy combined with neck SPECT/CT procedure. Planar images (early and delayed), US and SPECT/CT image sets were evaluated for adenoma localization at the neck and thorax. Regions of interest (ROIs), equal sized, were selected and compared, over the hyperfunctioning parathyroid tissue (accumulated impulses-counts value) and over the contralateral lobe of the thyroid gland (control counts value). Results: The ultrasonography detected 24 positive findings. The late phase of planar scan detected 26 positive findings. SPECT/CT presented with bigger detection rate than late planar phase or US (75.6%, 63.4%, 61.5%) and with higher sensitivity (100%, 83.8%, 77.4%), respectively. Conclusion: The SPECT/CT study seems reliable, sensitive and with added value in diagnosing hyperparathyroidism as a complementary method to planar scintigraphy. US as compatible method, should be performed prior the scintigraphy protocols.

Dermal Calcium Loss Is Not the Primary Determinant of Parathyroid Hormone Secretion during Exercise.

Exercise can cause a decrease in serum ionized calcium (iCa) concentration, which stimulates parathyroid hormone (PTH) secretion and activates bone resorption. We postulated that dermal Ca loss during cycling exercise is the major determinant of the serum iCa, PTH, and bone resorption (C-terminal telopeptide of type 1 collagen [CTX]) responses. To investigate this, women (n = 13) and men (n = 12) age 18 to 45 yr performed the same exercise bout under cool (18°C) and warm (26°C) conditions. Exercise was 60 min of cycling at ~75% of peak aerobic power. Sweat samples were obtained during exercise using a skin patch method, and blood samples were obtained before and during exercise and during 60 min of recovery. Sweat volume and estimated sweat Ca loss were 50% higher for the warm condition than the cool condition. Despite this, there were no differences between thermal conditions in the changes (mean, 95% confidence interval [95% CI]) in iCa (cool, -0.07 mg·dL; 95% CI, -0.16 to 0.03); warm, -0.07 mg·dL; 95% CI, -0.20 to 0.05), PTH (cool, 34.4 pg·mL; 95% CI, 23.6-45.2; warm: 35.8 pg·mL; 95% CI, 22.4-49.1), or CTX (cool, 0.11 ng·mL; 95% CI, 0.08-0.13; warm, 0.15 ng·mL; 95% CI, 0.11-0.18). Adjusting for exercise-related shifts in plasma volume revealed a marked decline in vascular iCa content in the first 15 min of exercise (cool, -0.85 mg·dL; 95% CI, -1.01 to -0.68; warm, -0.85 mg·dL; 95% CI, -1.05 to -0.66), before substantial sweat Ca loss had occurred. This indicates that dermal Ca loss was not the primary trigger for the increases in PTH and CTX during exercise. Further research is necessary to understand the causes and consequences of the disruption in Ca homeostasis during exercise and specifically the extravascular shift in iCa.

SUN-514 Severe Hypophosphatemia and Worsening Secondary Hyperparathyroidism Following Treatment with Denosumab

Introduction We present a case of a patient with osteoporosis and chronic kidney disease (CKD)-induced secondary hyperparathyroidism who developed severe hypophosphatemia and increasing parathyroid hormone (PTH) level after receiving Denosumab. Clinical Case 90-year-old male with CKD stage 3 presented for hyperparathyroidism evaluation in 2015. Baseline GFR was 39 - 47 ml/min/1.73 m2. PTH was 320 pg/ml (8 - 97 pg/ml) with normal calcium and low vitamin D (25-D) 14 ng/ml (30 - 100 ng/ml). Repeat PTH was 299 pg/ml; 25-D 23 ng/ml and 24-hr urine calcium was 8 mg (100 - 300 mg). Hyperparathyroidism was concluded to be due to CKD and Vitamin D deficiency. Vitamin D was replaced and PTH decreased to 262 pg/ml. With fragility fracture history, dual-energy X-ray absorptiometry (DXA) scan was obtained and resulted with a T-score of -2.8 SD at the femoral neck. Denosumab (60 mg) was started after 25-D normalized in 3/2016. Follow-up laboratory analysis in 8/2016 revealed PTH 512 pg/ml, calcium 8.9 mg/dl (8.5 - 10.1 mg/dl), 25-D 44.7 ng/ml and phosphate 1.3 mg/dl (2.5 - 4.5 mg/dl), previously 2.1 mg/dl. Alkaline phosphate 104 U/l (45 - 117 U/l), calcitriol 63.9 pg/ml (19.9 - 79.3 pg/ml) and fibroblast growth factor 23 (FGF-23) 188 RU/ml (44 - 215 RU/ml). 24-hr urine calcium was 27 mg and phosphate >90 mg/dl. Serum phosphate improved with supplementation and Cinacalcet started for high PTH. After the second Denosumab injection, low phosphate (1.2 mg/dl) recurred and PTH remained high (510 pg/ml). With recurrent effects, Denosumab was switched to bisphosphonate as GFR was stable >40 ml/min/1.73 m2. PTH normalized to 78 pg/ml and phosphate stable (2-2.4 mg/dl) on Cinacalcet and off Denosumab. Discussion Hypophosphatemia is a rare side effect of Denosumab, a monoclonal antibody to RANK-L. PTH mildly increase with Denosumab secondary to hypocalcemia. In our patient, there was a significant rise in PTH level and a decline in phosphate following Denosumab administration with no effect on calcium level. There are very few reports of these combined adverse events in the literature. The proposed mechanism is that the irreversible blockade by Denosumab results in low bone turnover which then causes increase in PTH and then increase urinary phosphate excretion. This mechanism can apply to CKD patients with secondary hyperparathyroidism when given a blocking agent like Denosumab, there is a further increase in PTH in the setting of low bone turnover. If not closely monitored, it can be detrimental. Elevated FGF-23 can downregulate 1-alpha-hydroxylase and increase urinary phosphate but unlikely in our patient given its normal level. Conclusion Severe hypophosphatemia may be a rare side effect of Denosumab, particularly in CKD patient with secondary hyperparathyroidism. Therefore, phosphate and PTH should be monitored closely after Denosumab administration to prevent adverse events.

OR30-5 Germline Ablation of G-Protein Subunit Alpha-11 in Mice Causes Hypercalcemia That Is Rectified by Treatment with Cinacalcet

G-protein subunit α-11 (Gα11) is a signalling partner of the calcium-sensing receptor (CaSR), which is a G-protein coupled receptor that plays a major role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion, urinary calcium excretion and skeletal development. Although loss-of-function point mutations of the GNA11 gene, which encodes Gα11, have been shown to increase plasma calcium concentrations and cause familial hypocalciuric hypercalcemia type 2 (FHH2), the overall contribution of Gα11 to the parathyroid, bone and renal regulation of calcium homeostasis remains to be established. The aim of this study was to characterise the impact of selective germline ablation of Gα11 on plasma concentrations of albumin-adjusted calcium (adj-calcium) and PTH, 24-hour urinary calcium excretion, and bone mineral density (BMD) in adult male and female heterozygous and homozygous Gna11 null C57BL/6N mice (n=13-16 mice per genotype), which had been previously generated by the International Mouse Phenotyping Consortium (IMPC). These mice were also treated with cinacalcet to assess whether this CaSR positive allosteric modulator can rectify any alterations in calcium homeostasis. All studies were conducted in accordance with institutional welfare guidelines. Male and female heterozygous Gna11 null (Gna11+/-) mice were viable and significantly hypercalcemic (plasma adj-calcium = 2.47±0.02 mM) compared to wild-type (WT) mice (plasma adj-calcium = 2.33±0.01 mM, p<0.0001). Gna11+/- mice showed no alterations in plasma PTH or 24-hour urinary calcium. In contrast, homozygous Gna11 null (Gna11-/-) mice showed reduced viability and the proportion of viable Gna11-/- mice was >25% less than would be expected from a Mendelian pattern of inheritance (p=0.01, Chi-squared analysis). Moreover, male and female Gna11-/- mice had significantly reduced body weight and were significantly more hypercalcemic (plasma adj-calcium = 2.70±0.02 mM) than Gna11+/- or WT mice (p<0.0001). Female Gna11-/- mice also showed significant increases in plasma PTH and 24-hour urinary calcium compared to female Gna11+/- and WT mice. However, no alterations in BMD were observed in male and female Gna11+/- or Gna11-/- mice. Administration of a single oral 30mg/kg cinacalcet dose significantly reduced plasma adj-calcium and PTH in Gna11+/- and Gna11-/- mice, and normalised plasma adj-calcium concentrations in Gna11-/- mice at 1-hour post-dose. Thus, these findings demonstrate that Gα11 plays a major role in regulating plasma calcium concentrations, but does not influence BMD, nor represent a key mediator of urinary calcium excretion. Furthermore, cinacalcet rectifies the hypercalcemia of Gna11 null mice, thus indicating that this CaSR-targeted compound may modulate parathyroid gland function in a Gα11-independent manner.

The Impact of Thyme and Rosemary on Prevention of Osteoporosis in Rats.

Osteoporosis poses an important public health problem which affects millions of people worldwide. There is a direct link between calcium deficiency in diet and induction of osteoporosis and bone loss. The current study was conducted to evaluate the protective effect of thyme (Thymus vulgaris L.) and rosemary (Rosmarinus officinalis L.) against osteoporosis in rats with low calcium intake. Essential oils of rosemary and thyme were analyzed. The experiment was carried out on growing male Sprague–Dawley rats; the experimental animals were divided into 5 groups: 1, control negative was fed standard balanced diet; 2, control positive was fed balanced diet with low calcium level (L Ca) (Ca 0.1% w/w); 3, (L Ca) + thyme powder (5% w/w); 4, (L Ca) + rosemary powder (5% w/w); 5, (L Ca) + orally administration with CaCO3 (27 mg/kg body weight). Blood samples were collected for different biochemical analyses in plasma (calcium (Ca), phosphorus (P), magnesium (Mg), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), malondialdehyde (MDA), parathyroid hormone (PTH), C-terminal telopeptide (CTX), and 1,25-(OH)2-vitamin D3). Femur mass, length, and bone mineral density (BMD) were recorded, and histopathological studies for femurs were examined. Low-calcium diet induced osteoporotic changes in positive control rats (decrease in Ca, vitamin D3, and BMD and increase in CTX, PTH, TNF-α, CRP, and MDA). Supplementation with thyme and rosemary inhibited significantly the development of bone loss, increased Ca and vitamin D3 in plasma, improved BMD, and also prevented the inflammation and oxidative stress (improved TNF-α, CRP and MDA) compared to the positive control. The histopathological examination of treated groups showed an improvement in bone histology and protection against bone loss. However, thyme powder showed more effective impact than rosemary. Our study demonstrates that thyme and rosemary effectively mitigated calcium deficiency-induced bone loss and maybe considered as promising candidates for preventing bone resorption and osteoporosis.

Bone Biomarker Response to Walking under Different Thermal Conditions in Older Adults.

This study aimed to determine whether exercise in a warm environment exaggerates the decrease in iCa and increases in PTH and CTX compared with a cool environment in older adults. Twelve women and men 61-78 yr old performed two identical 60-min treadmill bouts at ~75% of maximal heart rate under warm and cool conditions. Serum iCa, PTH, and CTX were measured every 15 min starting 15 min before and continuing for 60 min after exercise. Sweat Ca loss was estimated from sweat volume and sweat Ca concentration. Sweat volume was low and variable; there were no differences in sweat volume or Ca concentration between conditions. iCa decreased after 15 min of exercise, and the change was similar in both conditions. Increases in PTH (warm: 16.4, 95% confidence interval [CI] = 6.2, 26.5 pg·mL; cool: 17.3, 95% CI = 8.1, 26.4 pg·mL) and CTX (warm: 0.08, 95% CI = 0.05, 0.11 ng·mL; cool: 0.08, 95% CI = 0.01, 0.16 ng·mL) from before to immediately after exercise were statistically significant and similar between conditions. Adjusting for plasma volume shifts did not change the results. The increases in PTH and CTX, despite the low sweat volume, suggest that dermal Ca loss is not a major factor in the decrease in iCa and increases in PTH and CTX observed during exercise in older adults.