Serum Intact Parathyroid Hormone Concentrations Research Articles

Increased levels of osteoprotegerin in hemodialysis patients.

Recently identified soluble circulating osteoprotegerin (OPG), a member of tumor necrosis factor receptor family, is the osteoclastogenesis inhibitory factor (OCIF). It acts as a "decoy" receptor for receptor activator of NF-kappaB ligand (RANKL) and antagonises RANKL/RANK activity. This way OPG exerts the protective effect on bone, which is also important in hyperparathyroidism. The studies measuring OPG levels in secondary hyperparathyroidism have shown contradictory results and inconsistent conclusions. The aim of our work was to evaluate OPG levels in hemodialysis patients and their correlation with the intensity of bone turnover, bone formation and bone resorption. Serum OPG levels, bone alkaline phosphatase activity (bALP) and beta-CrossLaps (CTx) were measured in a control group (n = 20, age 30+/-6.7 years) and in two groups of dialysis patients: the first group with serum intact parathyroid hormone (iPTH) concentration below 200 pg/ml (n = 28, age 62.6+/-14.8 years) and the second group with iPTH concentration above 200 pg/ml (n = 16, age 63.7+/-14.8 years). Compared to controls, serum OPG levels were 6.4-fold higher in dialysis patients. OPG levels in patients with high PTH were approximately 1.2-fold higher than in the low-PTH group. OPG correlated weakly with bALP (r = 0.277, p = 0.153), as well as with CTx (r = 0.018, p = 0.929) in the low-PTH group, and there was an insignificant negative correlation in the high-PTH group (r = -0.145, p = 0.593 and r = -0.219, p = 0.416, respectively). In conclusion, 6.4-fold increase in OPG might protect bone against intensive bone loss in hemodialysis patients, but this increase is probably not mediated by the increased bone formation; rather, it seems to be the consequence of the imbalance of bone kinetics in renal disease. The precise role of OPG in the pathogenesis of renal osteodystrophy remains unknown and establishing it requires further studies.

Low serum concentrations of 25-hydroxyvitamin D in young adult Japanese women: a cross sectional study

OBJECTIVES: The vitamin D nutrition status of young adult women is unclear, but a recent preliminary report suggested that they may have vitamin D insufficiency. This study assessed the serum concentrations of 25-hydroxyvitamin D (25[OH]D), an index of vitamin D nutrition status, in young adult Japanese women in comparison with those in older women and investigated whether serum 25(OH)D concentrations are associated with other calcium-related hormones and bone mass. METHODS: A cross sectional study of 77 healthy women, age 19 to 66 y, working in nursing homes in Japan was conducted in the winter of 1999 and 2000. The investigation included blood tests, forearm bone mass measurements, and a lifestyle questionnaire. RESULTS: The mean serum 25(OH)D concentration in women younger than 30 y was 34.0 nmol/L (standard deviation [SD] = 11.0) and significantly lower than that in women 30 y and older (50.0 nmol/L, SD = 14.4). The proportion of subjects younger than 30 y who had serum 25(OH)D concentrations less than 30 nmol/L was 42.1% and was significantly higher ( P < 0.001) than the proportion of those 30 y and older (10.3%). There was a weak but significant linear association between serum 25(OH)D concentrations and forearm bone mineral content ( R 2 = 0.114, P = 0.0052) but not between serum 25(OH)D concentrations and bone mineral density. The association held after adjusting for body weight ( R 2 = 0.139, P = 0.0111). Serum intact parathyroid hormone concentrations were within the normal range and not associated with serum 25(OH)D concentrations. CONCLUSIONS: Serum 25(OH)D concentrations in young adult Japanese women (<30 y old) are lower than those of older adult women (30 to 66 y), and lower serum 25(OH)D concentrations are likely associated with lower forearm bone mineral content.

Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density

Vitamin D deficiency leads to secondary hyperparathyroidism, which has a negative effect on bone metabolism in the elderly. Puberty is an important time of bone metabolism and growth. The effect of serum 25-hydroxyvitamin D [25(OH)D] concentrations on parathyroid hormone concentrations and bone mineral density (BMD) has not been well studied cross-sectionally in adolescents. We studied the effect of vitamin D status on serum intact parathyroid hormone (iPTH) concentrations and bone metabolism in adolescents. One hundred seventy-eight healthy female adolescents (aged 14-16 y) volunteered for this study, which was conducted in Finland (Helsinki, 60 degrees N) during the winter. Forearm BMD at radial and ulnar sites was measured by dual energy X-ray absorptiometry. The determinants of different variables were studied by use of regression models. On the basis of the relation between serum 25(OH)D and iPTH concentrations, serum 25(OH)D concentrations > approximately 40 nmol/L were needed to keep serum iPTH concentrations low. One hundred ten subjects (61.8%) had serum 25(OH)D concentrations < or =40 nmol/L. Twenty-four subjects (13.5%) were considered vitamin D deficient when the serum 25(OH)D concentration of 25 nmol/L was used as a cutoff. Subjects with serum 25(OH)D concentrations < or =40 nmol/L had low mean forearm BMD values at both the radial (P = 0.04) and ulnar (P = 0.08) sites. A large percentage of adolescent females have low vitamin D status during the winter in Finland, which seems to have negative effects on bone health.

Hypercalciuria in children with febrile convulsions.

The purpose of the present study was to investigate whether idiopathic hypercalciuria may be implicated in the pathogenesis of febrile convulsions. We studied 38 children (22 boys) with febrile convulsions (mean (+/- SD) age 3.25 +/- 1.09 years) and 45 healthy children (28 boys) of similar age who served as controls. Twenty-four hour urine calcium and phosphate, as well as serum calcium, phosphate, alkaline phosphatase and intact parathyroid hormone (PTH) concentrations were determined. Hypercalciuria (urine Ca >4.0 mg/kg bodyweight per 24 h) was found in nine children with febrile convulsions (23.7%) and in three controls (6.7%). Hypercalciuric children excreted significantly more phosphate in their urine (37.0 +/- 11.6 mg/kg bodyweight per 24 h) than normocalciuric children (18.7 +/- 8.7 mg/kg bodyweight per 24 h) and controls (20.2 +/- 7.6 mg/kg bodyweight per 24 h). They also had higher serum intact PTH concentrations (49.87 +/- 15.36 pg/mL) than normocalciuric (35.39 +/- 15.67 pg/mL) and control children (28.21 +/- 14.00 pg/mL). According to the calcium-loading test, eight of nine children with hypercalciuria had the renal type of the disorder. Furthermore, hypercalciuric children had significantly more convulsive episodes (2.77 +/- 1.98) than normocalciuric children (1.86 +/- 1.24). Our results suggest that renal hypercalciuria may be implicated in the pathogenesis of febrile convulsions.

Biphasic Changes in Nitric Oxide Generation in Hemodialyzed Patients with End-Stage Renal Disease Treated with Recombinant Human Erythropoietin

Background: Use of recombinant human erythropoietin (rHuEpo) in patients with end-stage renal disease (ESRD) improves anemia and reduces the need for blood transfusions. However, one third of patients on rHuEpo develop hypertension, aggravation of preexistent hypertension, or other complications. Nitric oxide (NO) plays a role in blood pressure (BP) regulation. Whether rHuEpo treatment in ESRD is accompanied by alterations in NO production was explored in patients undergoing hemodialysis. Methods: Of 121 consecutive patients in a hemodialysis clinic, 107 were treated with rHuEpo and 14 were untreated. Plasma was collected before and after hemodialysis for quantification of nitrite and nitrate (NOx). Findings were correlated with various routinely monitored parameters. Results: Predialysis NOx levels were lower in the treated than the untreated group; postdialysis NOx levels were virtually the same. Thus, the change was less in the treated group. Urea reduction ratios (URR) and ultrafiltrate volumes were similar. The mean predialysis systolic BP was higher in the treated group than in the untreated group. The dose of rHuEpo did not correlate with the plasma NOx or the predialysis BPs. No correlation was found between NOx levels and Hb or gender. Of the 107 treated patients, 12 had an increased postdialysis NOx without differences in ultrafiltrate volumes or URR. This group had higher total serum calcium levels, faster pulses, and greater BP reductions than other treated patients. No difference was found in the use of calcium-channel blockers and serum phosphorus and intact parathyroid hormone concentrations did not differ significantly among these groups. Conclusions: Intermittently hemodialyzed ESRD patients treated with rHuEpo accumulate less NOx in the plasma before dialysis but generate more NOx during dialysis than untreated patients. About 11 % of treated patients generated excessive amounts of NOx, thereby maintaining plasma concentrations at the predialysis level or higher. This group experienced significant hemodynamic consequences characteristic of the excessive action of NO.

Biphasic changes in nitric oxide generation in hemodialyzed patients with end-stage renal disease treated with recombinant human erythropoietin.

Use of recombinant human erythropoietin (rHuEpo) in patients with end-stage renal disease (ESRD) improves anemia and reduces the need for blood transfusions. However, one third of patients on rHuEpo develop hypertension, aggravation of preexistent hypertension, or other complications. Nitric oxide (NO) plays a role in blood pressure (BP) regulation. Whether rHuEpo treatment in ESRD is accompanied by alterations in NO production was explored in patients undergoing hemodialysis. Of 121 consecutive patients in a hemodialysis clinic, 107 were treated with rHuEpo and 14 were untreated. Plasma was collected before and after hemodialysis for quantification of nitrite and nitrate (NOx). Findings were correlated with various routinely monitored parameters. Predialysis NOx levels were lower in the treated than the untreated group; postdialysis NOx levels were virtually the same. Thus, the change was less in the treated group. Urea reduction ratios (URR) and ultrafiltrate volumes were similar. The mean predialysis systolic BP was higher in the treated group than in the untreated group. The dose of rHuEpo did not correlate with the plasma NOx or the predialysis BPs. No correlation was found between NOx levels and Hb or gender. Of the 107 treated patients, 12 had an increased postdialysis NOx without differences in ultrafiltrate volumes or URR. This group had higher total serum calcium levels, faster pulses, and greater BP reductions than other treated patients. No difference was found in the use of calcium-channel blockers and serum phosphorus and intact parathyroid hormone concentrations did not differ significantly among these groups. Intermittently hemodialyzed ESRD patients treated with rHuEpo accumulate less NOx in the plasma before dialysis but generate more NOx during dialysis than untreated patients. About 11% of treated patients generated excessive amounts of NOx, thereby maintaining plasma concentrations at the predialysis level or higher. This group experienced significant hemodynamic consequences characteristic of the excessive action of NO.

Prednisolone induces an increase in serum calcium concentration: possible involvement of the kidney, the bone, and the intestine.

To evaluate the early effect of glucocorticoids on calcium metabolism, 15 subjects aged 22-58 years (5 males, 10 females) with chronic glomerulonephritis were orally treated with 40 mg daily of prednisolone. Five of these subjects were diagnosed with nephrotic syndrome and none had a serum creatinine concentration of more than 1.4 mg/dl. Serum specimens and 24-hour urine specimens were obtained just before and 24 hours after a single oral dose of prednisolone. Serum calcium, ionized calcium, phosphate, intact parathyroid hormone (PTH), intact osteocalcin and 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), and urinary excretion of calcium, phosphate, and deoxypyridinoline were measured. Both serum calcium and ionized calcium concentrations were significantly increased from 4.39 +/- 0. 10 to 4.47 +/- 0.09 mEq/liter (P = 0.037) and from 2.48 +/- 0.04 to 2.55 +/- 0.04 mEq/liter (P = 0.002), respectively, 24 hours following a single oral dose of prednisolone. Serum intact PTH concentration slightly decreased, but the difference was not significant by statistical analysis. Serum intact osteocalcin concentration was markedly suppressed. In contrast, no significant changes were observed in urinary excretion of deoxypyridinoline. Serum 1,25(OH)(2)D(3) concentration measured in five patients was significantly increased. No significant changes in urinary excretion of calcium was observed in the face of these findings. It thus follows that a single oral dose of prednisolone administration increases serum calcium and ionized calcium concentrations, possibly mediated by suppressed bone formation, increased intestinal absorption of calcium, and impaired urinary excretion of calcium.

PHEX expression in parathyroid gland and parathyroid hormone dysregulation in X-linked hypophosphatemia

X-linked hypophosphatemia (XLH), a renal phosphate (Pi) wasting disorder with defective bone mineralization, is caused by mutations in the PHEX gene (a Pi-regulating gene with homology to endopeptidases on the X chromosome). Parathyroid hormone (PTH) status in XLH has been controversial, with the prevailing belief that hyperparathyroidism develops in response to Pi therapy. We report a 5-year-old girl with XLH (patient 1) who had significant hyperparathyroidism at presentation, prior to initiation of therapy. We examined her response to a single oral Pi dose, in combination with calcitriol, and demonstrated a rise in serum concentration of intact PTH, which peaked at 4 h and paralleled the rise in serum Pi concentration. We also present two other patients whose parathyroid glands were analyzed for PHEX mRNA expression following parathyroidectomy. Patient 2 had autonomous hyperparathyroidism associated with chronic renal insufficiency, and patient 3, with XLH, developed autonomous hyperparathyroidism after 8 years of therapy with Pi and calcitriol. Following parathyroidectomy, patient 3 exhibited an increase in both serum Pi concentration and renal Pi reabsorption. The abundance of PHEX mRNA, relative to beta-actin mRNA, in parathyroid glands from patients 2 and 3 was several-fold greater than that in human fetal calvaria, as estimated by ribonuclease protection assay. In summary, we have shown that hyperparathyroidism can be a primary manifestation of XLH and that PHEX is abundantly expressed in the parathyroid gland. Given that PHEX has homology to endopeptidases, we propose that PHEX may have a role in the normal regulation of PTH.

Technetium-99m Sestamibi Scintigraphy and Bone Densitometry in Primary Hyperparathyroidism

To review our recent experience with technetium-99m sestamibi scintigraphy in identification and localization of parathyroid adenomas and to determine bone mineral loss associated with primary hyperparathyroidism. Thirty-two double-phase technetium-99m sestamibi scans were obtained in 26 patients (22 female and 4 male patients; age range, 14 to 78 years). Serum calcium and intact parathyroid hormone concentrations were measured before scintigraphy. Histopathologic correlation was obtained in all patients who underwent a surgical procedure. Seventeen patients underwent bone densitometry studies of the lumbar spine and hip with use of dual-energy x-ray absorptiometry. Of the 32 scans, 17 (53%) were suggestive of a parathyroid adenoma ("positive"). In these patients, the mean serum calcium concentration was 2.68 mmol/L and the mean serum parathyroid hormone concentration was 669 pg/mL. Overall, one false-negative scan and one false-positive scan were encountered. The overall sensitivity for surgically proven detection and localization of parathyroid adenoma was 90%. The bone density measurements in patients with positive scans were substantially lower in the lumbar spine (mean T score, 2.9) and in the hip (mean T score, 2.1) in comparison with normal control subjects and significantly lower than in those with a negative scan (spine, P = 0.011; hip, P = 0.015). Double-phase technetium-99m sestamibi scintigraphy is highly sensitive and useful in detection and localization of parathyroid adenomas. Patients with primary hyperparathyroidism lose bone mineral from both cortical and cancellous bone sites.

Parathyroid autotransplantation with total thyroidectomy for thyroid carcinoma: Long-term follow-up of grafted parathyroid function

Background: Permanent hypoparathyroidism is a major complication of thyroidectomy. Autotransplantation of parathyroid glands has been attempted to prevent this complication. However, no direct data have been available to assess grafted parathyroid function after long-term follow-up in terms of the serum intact parathyroid hormone (PTH) concentration. Methods: Eighty-four consecutive patients with differentiated thyroid carcinoma who underwent total thyroidectomy and bilateral modified neck dissection from 1992 to 1996 were enrolled. They concomitantly underwent total parathyroidectomy and autotransplantation of all parathyroid glands to the pectoralis major muscle. The serum intact PTH concentration was periodically measured as an index of grafted parathyroid function. Results: The mean follow-up was 34 months. In all autotransplanted patients serum intact PTH concentrations fell below detectable limits immediately after surgery. They were restored to the normal range within 1 month postoperatively and were maintained during observation in 80 (95%) of 84 patients. Seventy-eight of 80 patients with normal intact PTH values were normocalcemic without any treatment and the remainder were normocalcemic with 1 μg of 1α-vitamin D3. Four hypoparathyroid patients were normocalcemic with 2 μg of 1α-vitamin D3. The postoperative average serum intact PTH concentration of patients having more than 2 autotransplanted parathyroid glands was almost equal to that of patients with preservation of the parathyroid glands in situ. The incidence of permanent hypoparathyroidism was inversely correlated with the number of autotransplanted parathyroid glands. Conclusions: The recovery patterns of the intact PTH concentration indicate that the glands were grafted successfully and functioned for a long period. This feasible method of parathyroid autotransplantation bears comparison with the previous reports in terms of the incidence of permanent postoperative hypoparathyroidism, and it can be performed simply and is reproducible. (Surgery 1999;125:504-8.)

Parathyroid autotransplantation with total thyroidectomy for thyroid carcinoma: Long-term follow-up of grafted parathyroid function

Background: Permanent hypoparathyroidism is a major complication of thyroidectomy. Autotransplantation of parathyroid glands has been attempted to prevent this complication. However, no direct data have been available to assess grafted parathyroid function after long-term follow-up in terms of the serum intact parathyroid hormone (PTH) concentration. Methods: Eighty-four consecutive patients with differentiated thyroid carcinoma who underwent total thyroidectomy and bilateral modified neck dissection from 1992 to 1996 were enrolled. They concomitantly underwent total parathyroidectomy and autotransplantation of all parathyroid glands to the pectoralis major muscle. The serum intact PTH concentration was periodically measured as an index of grafted parathyroid function. Results: The mean follow-up was 34 months. In all autotransplanted patients serum intact PTH concentrations fell below detectable limits immediately after surgery. They were restored to the normal range within 1 month postoperatively and were maintained during observation in 80 (95%) of 84 patients. Seventy-eight of 80 patients with normal intact PTH values were normocalcemic without any treatment and the remainder were normocalcemic with 1 μg of 1α-vitamin D 3. Four hypoparathyroid patients were normocalcemic with 2 μg of 1α-vitamin D 3. The postoperative average serum intact PTH concentration of patients having more than 2 autotransplanted parathyroid glands was almost equal to that of patients with preservation of the parathyroid glands in situ. The incidence of permanent hypoparathyroidism was inversely correlated with the number of autotransplanted parathyroid glands. Conclusions: The recovery patterns of the intact PTH concentration indicate that the glands were grafted successfully and functioned for a long period. This feasible method of parathyroid autotransplantation bears comparison with the previous reports in terms of the incidence of permanent postoperative hypoparathyroidism, and it can be performed simply and is reproducible. (Surgery 1999;125:504-8.)

High bone turnover in the elderly

Objectives: To document lifestyle-associated variations in biochemical markers of bone metabolism in advanced age. Study Design: Cross-sectional study. Setting: Department of Geriatrics, University Hospital, Basel, Switzerland. Subjects: Three hundred twelve ambulatory and 193 institutionalized men and women, aged 54 to 99yrs. Outcome Measurements: Biochemical markers of bone resorption (urinary deoxypyridinolin and N-telopeptides), serum vitamin D metabolites, and serum intact parathyroid hormone (iPTH) concentrations were assessed. Mean values of all parameters were correlated with a six-grade activity score. Physical activity score reflected the degree of weight bearing, ranging from walking independently to primarily bed-bound. Ambulatory subjects were measured in summertime and institutionalized subjects in wintertime to accentuate seasonality of vitamin D hormone levels. Results: Excretion of bone resorption markers was significantly higher in the institutionalized and physically inactive patients compared with those who were ambulatory and physically active ( p = .0001). Vitamin D deficiency (25-hydroxyvitamin D of <12ng/mL) was present in 86% of institutionalized and 15% of ambulatory subjects, and 1,25-dihydroxyvitamin D serum concentrations were lower in institutionalized than in ambulatory subjects ( p = .0001). Mean serum concentrations for iPTH were similar for both the institutionalized and ambulatory groups. When subjects were arranged according to activity score, mean excretion of urinary bone resorption markers increased with degree of inactivity. Conclusion: Despite the difference in vitamin D metabolites, iPTH serum concentrations did not differ significantly between the institutionalized and ambulatory groups. However, institutionalized and physically inactive participants had markedly elevated excretion of urinary bone resorption markers compared with ambulatory and physically active subjects. These results suggest that high bone turnover in the elderly may be caused by physical inactivity related to low mechanical loading rather than secondary hyperparathyroidism.

Secondary hyperparathyroidism is an expected consequence of parathyroidectomy for primary hyperparathyroidism: A prospective study

Background: Parathyroidectomy for primary hyperparathyroidism (PHPT) can cause secondary hyperparathyroidism, with increased serum parathyroid hormone (PTH) and normal or low serum calcium concentrations. Methods: A prospective study investigated 78 consecutive patients who underwent exploration for PHPT. Serum intact PTH and total calcium concentrations were measured the evening after operation and ionized Ca ++ the following morning. These levels were reassayed 1 week later. Results: Before operation, the mean PTH level was 138 ± 15 pg/mL, total calcium concentration was 11.6 ± 0.1 mg/dL, and ionized Ca ++ concentration was 1.44 ± 0.02 mmol/L. On the night of the operation, the PTH level was 11 ± 2 pg/mL, and the total calcium concentration was 8.9 ± 0.1 mg/dL. Fifty-five patients had hypoparathyroidism, with a PTH level less than 10 pg/mL. The day after the operation, the ionized Ca ++ level was 1.14 ± 0.01 mmol/L. One week later, PTH, ionized Ca ++, and total serum calcium concentrations returned to normal levels. In 9 patients (12%), PTH levels were increased (98 ± 16 pg/mL), although ionized Ca ++ concentrations were normal (1.18 ± 0.02 mmol/L), demonstrating secondary hyperparathyroidism. Risk factors for postoperative secondary hyperparathyroidism included older age, symptomatic hyperparathyroidism, higher preoperative PTH and alakaline phosphatase levels, and lower serum phosphorous levels. In 70% of these patients, PTH levels returned to normal in 3 to 12 months. Conclusions: Secondary hyperparathyroidism occurs in 12% of patients after surgical treatment of PHPT. It is transient, possibly compensating for relative hypocalcemia. (Surgery 1998;124:1021-7.)

Long-term follow-up after subtotal parathyroidectomy in patients with renal failure.

The most appropriate type of surgery for hyperparathyroidism secondary to renal failure remains controversial. We report a 5-year experience of patients with hyperparathyroidism secondary to end-stage renal disease who underwent subtotal parathyroidectomy. We believe that this is the procedure of choice, offering several advantages over total parathyroidectomy with and without reimplantation. Retrospective review. Review of 14 consecutive renal failure patients who underwent subtotal parathyroidectomy by one surgeon (A.K.) was performed. Follow-up ranged from 4 to 54 months. All patients were receiving chronic maintenance dialysis. All patients came to surgery with clinical symptoms of parathyroid bone disease, elevated serum calcium levels (10.1-12.4 mg/dL), and intact parathyroid hormone levels (619-4160 pg/mL), despite maximal medical therapy. At exploration four glands were identified in all patients and three and a half were removed. All patients experienced symptomatic relief postoperatively with normalization or near-normalization of serum calcium concentration and intact parathyroid hormone concentrations. One patient developed recurrent disease 4 months after surgery, and on re-exploration a supernumerary substernal gland was identified. A second patient developed recurrent symptoms 4 years after surgery and at the time of this writing was awaiting re-exploration. All patients had either resolution of or marked improvement in their subjective complaints. There have been no cases of permanent hypoparathyroidism. We believe that subtotal parathyroidectomy is the best procedure for patients with refractory symptoms of secondary hyperparathyroidism.

Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure

To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. Double blind, prospective, randomised, placebo controlled study. 17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. 176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. 132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.

Serum intact parathyroid hormone in a random population sample of men and women: relationship to anthropometry, life-style factors, blood pressure, and vitamin D.

Intact parathyroid hormone (PTH) in serum was determined in a random population sample and was related to age, sex, body composition, life-style factors, blood pressure, blood lipids, plasma fibrinogen, and serum IGF-1, osteocalcin, and vitamin D. Within the framework of the WHO MONICA Project in the city of Göteborg, Sweden, 181 men and 166 women aged 25-64 years were studied. Intact PTH concentrations varied with age but were similar in both sexes (range 4-82 ng/liter) [mean (+/- SD) 23.8 +/- 10.4 ng/liter in men and 25.1 +/- 10.6 ng/liter in women]. Intact PTH concentrations increased with increasing age, body mass index, systolic blood pressure, and 1,25(OH)2D3 and decreased with increasing 25(OH)D3 in all subjects. Additionally, in men, intact PTH correlated positively to diastolic blood pressure and negatively to coffee consumption. In women, PTH also correlated negatively to smoking and IGF-1. In a multivariate analysis including all variables, age lost its significance. In both sexes there were independent positive relations between intact PTH and body mass index and 1,25(OH)2D3, and negative relations between PTH and smoking habits as well as 25(OH)D3; among men there was also negative relations between PTH and coffee consumption. The results indicate that life-style factors such as smoking and coffee consumption decrease the serum concentration of intact PTH, and the same effect is seen in individuals with low body mass index. Coffee intake, smoking, and low body mass index are also known to adversely affect bone mineral content, highlighting the relationship between PTH and bone metabolism.

Rapid Correction of Metabolic Acidosis in Chronic Renal Failure: Effect on Parathyroid Hormone Activity

To investigate the effect of rapid correction of chronic metabolic acidosis on circulating intact parathyroid hormone (I-PTH) activity by free calcium clamp in chronic renal failure, 18 patients were enrolled in this study. Metabolic acidosis was corrected by continuous bicarbonate infusion while plasma ionized calcium was clamped at the preinfusion level throughout the entire procedure. The plasma pH, bicarbonate, total CO2, sodium, serum total calcium and 1,25(OH)2 vitamin D3 levels increased significantly while serum concentrations of I-PTH, alkaline phosphatase and albumin showed significant decreases after bicarbonate infusion. The plasma ionized calcium, potassium, serum magnesium and inorganic phosphorus levels showed no significant difference before and after bicarbonate infusion. These results demonstrate that rapid correction of metabolic acidosis attenuates circulating PTH activity in chronic renal failure and may underline the importance of maintaining normal acid-base homeostasis particularly in the presence of secondary hyperparathyroidism.

Osteoporosis, Metabolic Aberrations, and Increased Risk for Vertebral Fractures After Partial Gastrectomy

A case-control study compared 129 men with earlier partial gastrectomy (operation during the period 1952-1961) with 216 men from a community-based population study. All were born 1910-1915 and the mean age was 72 years. Men with a previous partial gastrectomy had vertebral fractures in 19% compared with 4% (P < 0.01) in the control population. Bone mineral density (BMD) in the right calcaneus measured with dual energy photon absorptiometry was 20% lower in men with a Billroth II operation (P < 0.001) and 8% lower with a Billroth I operation (ns). In comparison with the controls, the men subjected to partial gastrectomy had higher serum concentrations of osteocalcin and alkaline phosphatase activity, a lower serum concentration of 25-hydroxyvitamin D (25OHD) and a lower body mass index (BMI). There were no difference in serum concentrations of free calcium, intact parathyroid hormone (PTH), or free thyroxine. The smoking prevalence was significantly higher in men with partial gastrectomy than in controls. Smokers had significantly lower serum concentrations of intact PTH and 25OHD than nonsmokers and also lower BMD and BMI. The relationships between intact PTH on one hand, and ionized calcium (inverse relationship) and osteocalcin (direct relationship) on the other were preserved in smokers, however. Gastroscopy was performed in 78 men with multiple biopsies in the gastric remnant and also in the small intestine. All but two subjects had chronic gastritis. Examination of sternal bone marrow smears showed that 40% of the Billroth-operated men lacked bone marrow reticular iron.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum ionized calcium, parathyroid hormone and related variables: effect of age and sex

This study was carried out in order to determine interrelationships of age and sex on parameters within the parathyroid endocrine system in healthy men and women. One hundred and fifteen normal subjects (70 females and 45 males) subdivided into three groups aged 25–35, 45–55 and 65–75 years were studied. Female subjects aged between 45 and 55 were further subdivided into two age-matched groups in relation to gonadal functional status. Serum intact parathyroid hormone (PTH) concentrations were measured using a two-site im-munoradiometric assay. We found that there was a significant decrease of serum ionized calcium with ageing only in men ( r = −0.666, P<0.001) and a significant increase of serum PTH with age in both men ( r = 0.488, P<0.001) and women ( r = 0.279, P<0.019). A significant inverse correlation was found between serum ionized calcium and PTH in male subjects ( r = −0.661, P<0.001) and in fertile females ( r = −0.353, P<0.037) but not in postmenopausal women or in the entire female population. Furthermore, we found a significant decline of serum phosphate ( r=−0.484, P<0.001) and TmP/GFR ( r=−0.492, P<0.001) with advancing age in men, but not in women. We believe that the decrease of serum ionized calcium, as a likely consequence of the physiological reduction of intestinal calcium absorption, is the pivotal factor responsible for the increased PTH levels we observed with advancing age. The phenomenon is clear in men and in premenopausal women, but is masked in the female sex at menopause by the effects of a shortage of oestrogen on the calcium-phosphorus metabolism. These may also be responsible for the differences observed between the two sexes as far as phosphate metabolism is concerned. In conclusion, this study has, for the first time, taken relationships between serum ionized calcium and PTH, over a wide age range, into consideration. The results obtained show a marked difference of serum ionized calcium values between sexes with ageing, while serum parathyroid hormone levels increase in both men and women. Important differences also exist, as far as phosphate metabolism is concerned, between males and females.

Low serum 25-hydroxyvitamin D concentrations and secondary hyperparathyroidism in middle-aged white strict vegetarians

The vitamin D status of vegetarians was studied in the winter. The groups studied were strict vegetarians (G1), lactovegetarians (G2), lactoovovegetarians eating some fish (G3), and vegetarians who were taking vitamin D supplements or who had been exposed to abundant sunlight during the last 6 mo (G4). A group of healthy women served as control subjects (C). The serum 25-hydroxyvitamin D [25(OH)D] concentration was significantly lower, the serum intact parathyroid hormone (S-iPTH) concentration significantly higher, and the dietary vitamin D intake significantly lower in G1 than in C. S-iPTH correlated negatively with serum 25(OH)D and dietary calcium intake. In conclusion, white strict vegetarians are at risk of vitamin D deficiency, at least in the winter, primarily because of a low dietary vitamin D intake, despite a normal sunlight exposure in summer. Low serum 25(OH)D concentrations are accompanied by high S-iPTH concentrations, which also are affected by a low calcium intake. The effect of these changes on bone health remains to be evaluated.