Effects of Lowering Dialysate Calcium Concentration on Mineral and Bone Disorders in Chronic Hemodialysis Patients: Conversion from 3.0 mEq/L to 2.75 mEq/L

Selection of a lower dialysate calcium concentration (DCa) can reduce calcium burden and prevent vascular calcification in hemodialysis patients. However, decreased DCa can worsen mineral and bone disorders. This 1‐year retrospective observational study evaluated 121 hemodialysis patients at Fukuoka Renal Clinic who underwent conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. The primary outcomes were changes in serum levels of calcium, phosphate, and parathyroid hormone (PTH). The effects of baseline serum calcium and PTH levels on changes in biochemical parameters were also determined. One year after DCa conversion, mean serum calcium level decreased, while serum phosphate, alkaline phosphatase, and PTH concentrations increased. The rate of achievement of target PTH was higher in patients with lower serum PTH level at baseline, while patients with higher baseline serum PTH level tended to exceed the upper limit of the PTH target range. Patients with higher baseline serum calcium concentration showed a greater decrease in serum calcium level and a greater increase in serum PTH level at 1 year. Patients with a lower baseline serum PTH level can benefit from optimal PTH control following conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. However, secondary hyperparathyroidism may be exacerbated in some patients with higher baseline serum calcium (Ca) and PTH levels. These results indicate that an individualized approach can maximize the benefits of Ca unloading after conversion to lower DCa.     

The influence of dialysate calcium on the therapeutic effects of sevelamer hydrochloride in hemodialysis patients with secondary hyperparathyroidism under treatment of intravenous vitamin d metabolites

The management of hyperphosphatemia is essential to treat secondary hyperparathyroidism and to prevent ectopic calcification. Sevelamer hydrochloride (sevelamer), a new phosphate binder that contains neither aluminum nor calcium, which could be theoretically beneficial for the management of hyperphosphatemia in dialysis patients with secondary hyperparathyroidism who are receiving intravenous vitamin D metabolites (maxacalcitol or calcitriol). To reduce calcium loads, a dialysate calcium concentration of 2.5 mEq/L is recommended by Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines. In Japan, a dialysate calcium concentration of 3.0 mEq/L prevails. We investigated the influence of dialysate calcium on the therapeutic effect of sevelamer in 40 hemodialysis patients who are under treatment of intravenous vitamin D metabolites for secondary hyperparathyroidism (VD(+)) and compared the results with those of 41 patients who had not received vitamin D metabolites (VD(-)). Serum phosphorus and calcium-phosphorus products showed no significant change by sevelamer in either the VD(+) subgroup of patients receiving hemodialysis with dialysate calcium of 2.5 mEq/L (DCa2.5) or those receiving hemodialysis with dialysate calcium of 3.0 mEq/L (DCa3.0), while serum phosphorus and calcium-phosphorus products decreased in both the VD(-) subgroups. Serum calcium decreased in the DCa2.5 subgroup and did not change in the DCa3.0 subgroup in both the VD(+) and the VD(-) subjects. Parathyroid hormone and alkaline phosphatase increased in the DCa2.5 subgroup and did not change in the Ca 3.0 subgroup in the VD(+) subjects. Serum calcium decreased in both subgroups in the VD(-) subjects. Parathyroid hormone obtained after sevelamer administration in the VD(-) group was within the target range of the K/DOQI guidelines. In conclusion, the concomitant use of sevelamer as a phosphate binder and the dialysate of calcium concentration of 2.5 mEq/L have possibilities for worsening secondary hyperparathyroidism in patients receiving intravenous vitamin D.     

Effect of salmon calcitonin on bone mineral density and calcium-phosphate metabolism in chronic hemodialysis patients with secondary hyperparathyroidism

The aim of the study was to evaluate the effect of salmon calcitonin on bone mineral density, parathyroid and thyroid C cells, and calcium-phosphate metabolism in chronic hemodialysis patients with uremic hyperparathyroidism. Forty five patients with serum 1-84 PTH >220 pg/ml were divided into 2 groups: group I (n = 25), treated with intranasal salmon calcitonin (200 IU, thrice a week) and control group II (n = 20). Patients received calcium carbonate (up to 6 g/d) alone or with aluminum hydroxide (up to 3 g/d) as phosphate binders; dialysate calcium was 1.75-2 mmol/l. The observation period was 12 months. The following parameters were measured: bone mineral density (BMD) with dual-energy X-ray absorptiometry in: lumbar spine (L2-L4), femoral neck and total body, before and after the study; serum endogenous calcitonin, before and after the study; serum PTH, alkaline phosphatase and total hydroxyproline, before and after 1, 3, 6, and 12 months; and serum calcium and phosphate monthly. During 12 months of the study, a substantial reduction in BMD was observed in all examined regions in group II (-2.8 +/- 2.1%; p<0.01 in L2-L4, -2.4 +/- 2.0%; p<0.01 in femoral neck, and -1.9 +/- 1.4%; p<0.01 in total body), whereas in group I a slight increase of bone mineral was noted, however insignificant. The inhibition of bone resorption was accompanied by a marked decrease in serum hydroxyproline. No changes in parathyroid activity were noted nor any decrease in serum phosphate. The treatment had no influence on serum endogenous calcitonin; initial concentrations were elevated in 47% of patients. CONCLUSION: Intranasal salmon calcitonin: 1) has no influence on bone mineralization in dialysis patients with uremic hyperparathyroidism; 2) has no significant effect on serum phosphate concentration; 3) provided adequate calcium supplementation doesn't stimulate parathyroid glands; 4) has no influence on endogenous calcitonin secretion.     

Effects of Lowering Dialysate Calcium Concentration on Bone Metabolic Markers in Hemodialysis Patients With Suppressed Serum Parathyroid Hormone: A Preliminary Study

Although the Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend a dialysate calcium concentration between 2.5 and 3.0 mEq/L, its optimal concentration remains unclear. A total of 53 hemodialysis patients with intact parathyroid hormone (PTH) levels <150 pg/mL were enrolled in this prospective observational study. A dialysate calcium concentration was converted from 3.0 to 2.75 mEq/L and bone metabolic markers including bone alkaline phosphatase (BAP) and tartrate‐resistant acid phosphatase‐5b (TRACP‐5b) were examined. After 3 months, serum corrected calcium levels decreased (P < 0.001), while serum intact PTH, BAP and TRACP‐5b levels increased (P < 0.05, P < 0.05 and P < 0.001, respectively). Multiple regression analyses showed that the amount of change in BAP was significantly associated with dialysis vintage (P < 0.01). In conclusion, the lowering of dialysate calcium concentration stimulated parathyroid gland and bone remodeling in hemodialysis patients with suppressed PTH, particularly with longer dialysis vintage.     

Peritoneal anionic transfers and their relationship with peritoneal transport and acid-base status

This study was designed to assess lactate and TCO2 transfers during PET and in 24-hour drained dialysate, relating them with the membrane transport type and acid-base status. Forty PETs were studied, performed in 23 clinically stable patients maintained on CAPD for 6.5 +/- 3 months using 35 mEq/l of lactated-based dialysate. No significant changes in plasma concentration of lactate and TCO2 were observed. Lactate gain (LG) was 51.91 +/- 4.86 and 220.82 +/- 22.61 mEq and TCO2 loss was 46.49 +/- 6.9 and 183.51 +/- 32.9 mEq during PET and 24 h respectively. When analyzed these transfers according to membrane transport characteristics (High/High-average group: HHAG and low/low-average group: LLAG), LG was significantly higher (53.94 +/- 3.7 vs 48.86 +/- 4.8 mEq during TEP p < 0.01, and 228.06 +/- 15.6 vs 209.96 +/- 27.2 mEq during 24 h p < 0.05). TCO2 loss was greater (48.66 +/- 7.15 vs 43.25 +/- 5.5 mEq p < 0.05 and 187.22 +/- 27.3 vs 177.93 +/- 35.3 during PET and 24 h respectively) in HHAG vs LLAG. When evaluating transfers according to patients' acid-base status (normal and acidotic group), no significant differences were found in LG, but there was a significant difference in TCO2 loss (47.7 +/- 5.9 vs 39.76 +/- 6.1 mEq p < 0.01). We did not observe significant differences in acid-base balance during PET according to membrane transport characteristics (HHAG vs LLAG). However, acid-base balance was more positive in acidotic patients' PET than in normal patients (9.87 +/- 6.6 vs 3.92 +/- 6.8 mEq p < 0.05). TCO2 loss during PET directly correlated with plasma TCO2 concentration pre-PET (r: 0.43, p < 0.01). However no significant correlation was found between plasma lactate levels and lactate gain during PET. In conclusion, the lactate gain and bicarbonate loss account for the net dialytic base balance during PET and 24 h. However, the peritoneal membrane transport characteristics as well as the acid-base status can determine a higher or lower aionic transfer (lactate and bicarbonate).     

A long-term comparative study of calcitriol versus alphacalcidol in patients with secondary hyperparathyroidism on hemodialysis

Calcitriol has traditionally been the most widely used treatment for secondary hyperparathyroidism (SHPT) in uremic patients. There are currently no crossover equivalence studies of alphacalcidol versus calcitriol establishing which of the two derivatives is more active and better tolerated. The objective of this study was to compare the long term effect on control of PTH of similar doses of alphacalcidol versus calcitriol in the treatment of SHPT in these patients. METHODS: We conducted a retrospective study on 21 hemodialysis patients with stable SHPT of varying severity treated with intravenous calcitriol. In July 2002, the pharmacy of the reference hospital decided to substitute calcitriol for alphacalcidol based on the similarity of the two drugs. The conversion was made substituting a similar amount of drug. Mean absolute serum levels and percentage change in PTH, calcium and phosphorus were compared between the two periods and at 0, 3, 6, 9, 12 and 15 months after starting treatment with alphacalcidol. Student's t-test for paired means was used to compare the values between the two periods. RESULTS: In the calcitriol period, mean PTH levels were 275.2 +/- 111.7 pg/ml. The mean dose of drug used was 1.7 +/- 0.8 mcg postdialysis, and serum calcium and phosphorus levels were 10.1 +/- 0,5 mg/dl and 5,2 +/- 0,9 mg/dl, respectively (p < 0.01). Mean dialysate calcium content was 2,9 +/- 0,3 mEq/l. In the alphacalcidol period, PTH increased (441.6 +/- 178.3 pg/ml) (p < 0.001) and the percentage of patients with PTH < 300 pg/ml decreased (24% at the end of the period), in spite of significantly increasing the mean drug dose (2,3 +/- 0,9 mcg postdialysis) (p < 0.05). Serum calcium levels did not show significant differences (10.2 +/- 0.7 mg/dl) (p = NS), but phosphorus control was improved (4,7 +/- 0,5 mg/dl) (p < 0.01). The percentage of patients with PTH < 300 pg/ml decreased progressively from the start of treatment with alphacalcidol from 75% to 24% at the end of follow-up. Our results seem to suggest that the dose of alphacalcidol and calcitriol are not equivalent and we need to increase the dose of alphacalcidol to obtain a similar result to calcitriol on suppression of PTH in uremic patients with SPTH.     

Effects of the selective oestrogen receptor modulator-raloxifene-on calcium and PTH secretory dynamics in women with osteoporosis

OBJECTIVES: A possible mechanism for the maintenance of bone mass by oestrogens and the selective oestrogen receptor modulator (SERM)-raloxifene-is an interaction with calciotropic hormones. We studied the effects of raloxifene on calcium-PTH homeostasis. PATIENTS AND MEASUREMENTS: Calcium and EDTA infusions were performed in 32 post-menopausal women with osteoporosis (BMD T score < - 2.5). This cross-sectional study was performed in the third year of the MORE (Multiple Outcomes of Raloxifene Evaluation) trial, a double-blind, placebo-controlled study. After an overnight fast, calcium glubionate (5 mg/kg BW*h), and after 2.5 h of test-free interval, Na3EDTA (40 mg/kg BW*h) were given intravenously. The duration of infusions was based on individual plasma total calcium before the calcium infusion (t = 0), the target calcium (2.60 and 1.95 mmol/l, respectively), and desired mean calcium change (0.010 mmol/L*min). Blood samples were taken at 0 and every 5 minutes of both infusions. Plasma PTH levels were fitted into an inversed sigmoidal relation with plasma calcium. The effect of raloxifene on calcium-PTH homeostasis was tested in linear regression models adjusted for age and BMI. Nine patients used placebo, 13 raloxifene 60 mg/day and 10 raloxifene 120 mg/day. RESULTS: Raloxifene use was associated with lower plasma albumin (40.7 +/- 1.8 vs. 38.0 +/- 2.0 and 38.5 +/- 2.3 g/l, for placebo, raloxifene 60 mg/day and raloxifene 120 mg/day, respectively, P = 0.01), lower plasma total calcium at t = 0 (2.28 vs. 2.24 and 2.21; +/- 0.07 mmol/L; P = 0.03), lower plasma total calcium at 50% of maximal PTH secretion (PTH set-point: 2.23 +/- 0.06 vs. 2.18 +/- 0.07 and 2.16 +/- 0.08 mmol/l, P = 0.06), and lower plasma non-suppressible PTH (0.84 +/- 0.19 vs. 0.75 +/- 0.10 and 0.73 +/- 0.05 pmol/l, P = 0.02). After correction for plasma albumin, the differences for plasma calcium at t = 0 and at PTH set-point were no longer significant. In contrast, the difference in PTH suppression during calcium load was not explained either by differences in plasma albumin or calcium. CONCLUSION: Raloxifene did not have any detectable effect on the PTH set-point. An effect on non-suppressible PTH secretion cannot be excluded.     

Pattern of bone mineral density in patients with sporadic idiopathic hypoparathyroidism

OBJECTIVE: Measurement of bone mineral density (BMD) in patients with hypoparathyroidism directly addresses the effect of chronic under-exposure of bone to PTH. Because post-thyroidectomy hypoparathyroidism is potentially complicated by the pre-existence of thyrotoxicosis and the need for postoperative thyroxine replacement, we have studied a large group of patients with sporadic hypoparathyroidism who have been followed up in our endocrine clinic. Studies conducted in limited number of patients with sporadic idiopathic hypoparathyroidism (SIH) have suggested an increase in BMD in such patients. In this current study, we have measured BMD in a large cohort of patients with SIH and have assessed the relationship of BMD with duration of disease and with the adequacy of treatment, as indicated by follow-up serum calcium, phosphate and alkaline phosphatase levels. DESIGN: Case control study and intra-group comparison. SUBJECTS: Forty-seven patients (M : F ratio 23 : 24) with SIH who had been reviewed during 2003-2004 in our endocrine clinic were recruited for this study. Their mean age (+/- SD) was 34.6 +/- 13.6 years and the duration from the time of initial diagnosis was 9.6 +/- 8.5 years. Forty-eight match healthy volunteers were recruited from hospital staff and from normocalcaemic relatives. METHODS: Bone mineral density was measured at total lumbar spine (L1-L4), hip and forearm by dual energy X-ray absorptiometry (DXA). The relationship of BMD was analysed with duration of disease symptoms (group I, < or = 1 year, group II, > 1 and < 5 years and group III, > or = 5 years) and mean serum total calcium observed during follow-up (group A, calcium < or = 1.79 mmol/l and group B, > or = 1.80 mmol/l). RESULTS: Patients with SIH showed significantly higher BMD at total lumbar spine and hip when compared to controls (1.098 +/- 0.187 vs. 0.936 +/- 0.131 g/cm2 and 0.967 +/- 0.141 vs. 0.882 +/- 0.149 g/cm2, P < 0.001 for both). BMD in the forearm was not significantly different in patients and controls. The age- and BMI-adjusted lumbar spine BMD showed correlation with duration of disease (r = 0.348 and P = 0.019). Patients with longer duration of hypoparathyroidism had higher BMD at lumbar spine (group I vs. group III, 0.951 +/- 0.132 vs. 1.156 +/- 0.180 g/cm2, P < 0.05). There was no significant correlation between BMD values in patients with SIH and their mean serum total calcium levels during the period of follow-up (r = 0.192, P = 0.206). Neither was the mean BMD significantly different between group A and B. Serum total alkaline phosphatase showed a significant negative correlation with BMD at lumbar spine (r = -0.445, P = 0.012). CONCLUSIONS: Patients with sporadic idiopathic hypoparathyroidism have increased mean BMD in the lumbar spine and hip but not in the forearm, compared to normal matched healthy controls. The increase in BMD is related to the duration of the disease rather than the serum calcium levels.     

Bone mass at final height in precocious puberty after gonadotropin-releasing hormone agonist with and without calcium supplementation

The aim of our longitudinal study was to evaluate bone mass in girls affected by central precocious puberty (CPP) that have reached final height, treated with GnRH agonist triptorelin (GnRHa), with or without calcium supplementation. We studied 48 Caucasian females affected by CPP (age at diagnosis, 7.19 +/- 0.96 yr), randomly assigned to two groups: group A (n = 21) treated with GnRHa and group B (n = 27) treated with GnRHa plus calcium gluconolactate and carbonate (1 g calcium/day in two doses) for at least 2 yr. Auxological parameters (standing height, weight, body mass index) and bone mineral density (BMD) at the lumbar spine [L2-L4, anteroposterior (AP)-BMD; lateral BMD; volumetric (v)BMD)] by dual-energy x-ray absorptiometry were evaluated at the beginning [chronological age (CA), 7.29 +/- 0.91 yr; bone age (BA), 8.80 +/- 1.24 yr] and end of treatment (CA, 11.27 +/- 0.97 yr; BA, 12.35 +/- 0.43 yr) and at final height (CA, 16.17 +/- 1.9 yr; BA, 16.93 +/- 0.98 yr, in each case >15 yr). Total bone mineral content, total BMD, and fat percentage were evaluated at the end of the study period using dual-energy x-ray absorptiometry. Final height was significantly higher than predicted height at diagnosis (159.9 +/- 6.3 cm vs. 152.9 +/- 9.6 cm; P < 0.05). Body mass index and fat percentage were not statistically different from control values. Densitometric values at final evaluation in groups A and B together were lower than in controls, but the differences were not statistically significant. The vBMD was significantly higher in group B than in group A at the end of treatment period (0.213 +/- 0.022 g/cm(3) vs. 0.192 +/- 0.021 g/cm(3); P < 0.01) and at final evaluation (0.246 +/- 0.023 g/cm(3) vs. 0.227 +/- 0.024 g/cm(3); P < 0.05). The percentage change (Delta%) between the start and end of treatment period in AP-BMD and vBMD was significantly higher in group B than in group A (Delta% AP-BMD: 20.36% +/- 1.10% vs. 16.16% +/- 1.90%, P < 0.01; Delta% vBMD: 19.08% +/- 3.52% vs. 9.26% +/- 5.15%; P < 0.01) and also between the start of treatment and final evaluation (Delta% AP-BMD: 61.23% +/- 1.61% vs. 56.97% +/- 1.45%, P < 0.01; Delta% vBMD: 36.69% +/- 5.01% vs. 28.01% +/- 5.76%, P < 0.01). In all our females with CPP treated with GnRHa, bone densitometric parameters were in the normal range for age and sex. However, bone mass achievement seemed to be better preserved in the group of patients supplemented with calcium.     

Renal ostodystrophy during the developing stage of maintenance dialysis in Transylvania. Early development of periarticular calcifications and beta 2 microglobulin amyloidosis in spite of a relatively good prevention of secondary hyperparathyroidism

BACKGROUND: Dialysis facilities have been introduced only recently in Transylvania with many limitations, in particular a standard high calcium dialysate, Al(OH)3 as phosphate binder and pharmacological doses of native vitamin D2, but neither CaCO3 nor 1 alpha hydroxylated vitamin D. Rheumatological complaints and metastatic calcifications were frequent, leading to suspect either overt hyperparathyroidism, adynamic bone disease or beta 2 microglobulin amyloidosis. AIMS OF THE STUDY: Evaluate the prevalence of radiological osteitis fibrosa, amyloid osteoarthropathy and periarticular calcification and their link with PTH secretion, phophocalcic disorders, acidosis, bone turn over, aluminum and beta 2 microglobulin accumulation in the dialysis population of Sibiu (Transylvania). METHODS: The clinical and radiological rheumatological data of the 49 uremic patients dialyzed in Sibiu since 1990 were reviewed as well as the monthly routine monitoring of their plasma phosphocalcic parameters. Furthermore in July 1994, 36 of them had an X rays of the hands for evaluation of subperiosteal resorption of the phalanges, periarticular calcifications and carpal cysts as well as a determination of plasma concentrations of intact PTH (normal range: 10-55; optimal range: 100-200 pg/ml), osteocalcin, bone alkaline phosphatase, aluminum and 25 OH vitamin D. RESULTS: The prevalence of subperiostal resorption of the phalanges was 8% and that of severe biological hyperparathyroidism (PTH > 400 pg/ml) 22%, whereas that of a relative hypoparathyroidism (PTH < 100 pg/ml) was 31%. Mean plasma concentrations of calcium was 2.07 +/- 0.15; of phosphate 2.50 +/- 0.35; of bicarbonate 15 +/- 2.0 mmol/l, of 25 OHD 30 +/- 20 ng/ml, of aluminum 1.1 +/- 0.5 mumol/l. Plasma PTH concentrations were negatively correlated to dialysis duration, and to plasma concentrations of aluminum, calcium and 25 OH vitamin D but not to those of phosphate and bicarbonate. Multivariate analysis showed however that only duration of dialysis and plasma aluminum concentration were independently and negatively correlated to plasma PTH concentrations. The prevalence of periarticular calcifications (26%) and of carpal cysts suggestive of beta 2 microglobulin amyloidosis (10%) were relatively high considering the young age of the population (42 years) and the short duration of dialysis (2.6 years). Patients with calcifications comparatively to those without calcifications were older, had longer duration on dialysis, higher prevalence of carpal cysts and higher plasma beta 2 microglobulin concentrations, lower plasma PTH (98 versus 313 pg/ml) and higher plasma aluminum concentration (1.3 versus 0.8 mumol/l). Patients with carpal cysts comparatively to those without cyst were older, had a longer duration on dialysis and a higher prevalence of periarticular calcifications. CONCLUSIONS: a) In spite of no use of 1 alpha hydroxylated vitamin D derivatives, and poor control of hyperphosphatemia and acidosis, hyperparathyroidism declined with duration of dialysis due to the use of a high dialysate calcium concentration, Al(OH)3 as sole phosphate binder and high supplement of native vitamin D. b) Considering the relative young age and short duration on dialysis, the prevalence of periarticular calcifications and carpal cysts were high. c) Calcifications were possibly favored by relative hypoparathyroidism and moderate aluminum overload. d) The association of periarticular calcifications and subchondrial cysts suggest a causal relationship.     

A slight decrease in renal function further impairs bone mineral density in primary hyperparathyroidism

BACKGROUND: The impairment of renal function can affect the clinical presentation of primary hyperparathyroidism (PHPT), increasing cardiovascular morbidity, fracture rate, and the risk of mortality. AIM: The aim of the study was to assess the differences in bone status in a series of consecutive patients affected by PHPT without overt renal failure at diagnosis grouped according to creatinine clearance (Ccr). METHODS: A total of 161 consecutive patients with PHPT were studied. They were divided into two groups based on Ccr. Group A had Ccr 70 ml/min or less (n = 49), and group B had Ccr greater than 70 ml/min (n = 112). PTH, total and ionized serum calcium; urinary calcium and phosphate; serum 25-hydroxyvitamin D3; serum and urinary bone markers; lumbar, forearm, and femoral bone mineral density (BMD) were evaluated. RESULTS: Patients in group A were older than those in group B (P < 0.0001). PTH levels did not differ in the two groups, whereas both urinary calcium and phosphorus were lower in group A than group B (P < 0.01). Lower BMD was evident in group A at lumbar spine (P < 0.002), forearm (P < 0.0001), and femur (P < 0.01). In asymptomatic PHPT, those with Ccr 70 ml/min or less had lower forearm BMD than patients with higher Ccr (P < 0.00001). When adjusting for age and body mass index in PHPT, BMD at each site persisted being lower (P < 0.05) in group A than group B. In all PHPT subjects, Ccr (beta = 0.29, P < 0.0005), age (beta = -0.27, P < 0.00001), and PTH levels (beta = -0.27, P < 0.0005) were all independently associated with forearm BMD. CONCLUSIONS: In PHPT a slight decrease in renal function is associated with more severe BMD decrease, independent of age, body mass index, and PTH levels. This association is also present in asymptomatic PHPT and strengthens the National Institutes of Health recommendations for surgery in patients with mild PHPT.     

Renal osteodystrophy (3); its treatment in dialysis patients

The prevalence and the clinical gravity of the various histopathological varieties of renal osteodystrophy in dialysis patients depends on the severity of both the aluminium intoxication and that of hyperparathyroidism. The prevalence of bone pains, fractures and hypercalcemias are the highest in adynamic bone diseases (ABD) with severe aluminium intoxication, then in osteitis fibrosa and mixed osteopathy, in the ABD with moderate aluminium intoxication and rare in the mild lesion in spite of similar moderate aluminium intoxication. In the absence of aluminium intoxication, hypercalcemia and hyperphosphatemia prevalence is higher only when intact PTH is more that 4 times the upper limit of normal. When PTH is between 1 and 2 folds the ULN this prevalence is null and bone mineral density is the highest. 2. The low turnover aluminic bone diseases (osteomalacic or adynamic) will be cured by long term deferoxamine treatment. The hazards of such treatment justify the performance of a bone biopsy to ensure the diagnosis. Their prevention relies on adequate treatment of tapwater and definitive exclusion of long term administration of aluminum phosphate binders. 3. Non aluminic osteomalacia will be treated according to the same guidelines given for the uremic patients before dialysis. 4. Non aluminic adynamic bone disease will be cured by means aiming at stimulating PTH secretion as discontinuing 1 alpha hydroxylated vitamin D derivatives, and, if there is no hyperphosphatemia by discontinuation of calcium supplement. In case of hyperphosphatemia in dialysis patients CaCO3 doses have to be nevertheless increased after the dialysate calcium concentration (DCa) has been decreased in order to induce a negative perdialytic calcium balance for PTH secretion stimulation. In the near future substitution of CaCO3 by non calcemic non aluminic phosphate binders will suffice. 5. Osteitis fibrosa due to hyperparathyroidism will be treated first by securing an optimal vitamin D repletion (bringing plasma 25OH vitamin D around 30 and 60 ng/ml or 75-150 nmol/l) and by correcting hypocalcemia and hyperphosphatemia by CaCO3 at high doses (3-12 g/day) taken with the meals. In case of hypercalcemia dialysate calcium concentration will be decreased to correct it or, in a near future, CaCO3 will be decreased to 3 g/day and hyperphosphatemia will be controlled by non calcemic, non aluminic phosphate binders. When hyperphosphatemia is controlled whereas plasma calcium is normal or low, 1 alpha hydroxylated vitamin D derivatives can be administered. 6. Instrumental parathyroidectomy should be considered when plasma levels of intact PTH remain above 7 folds the upper limit of normal whereas hyperphosphatemia persists and hypercalcemia occurs in order to prevent thining of the corticals and subsequent fracture risk. In case of previous exposition to aluminum, a deferoxamine test and/or a bone biopsy will be performed to decide a long term DFO treatment before the parathyroidectomy in order to prevent the transformation of a mixed osteopathy into an aluminic adynamic bone disease. 7. The difficulty of hyperparathyroidism control in dialysis patients is due to poor compliance to phosphate binders and to irreversible parathyroid hyperplasia with occured before the dialysis stage. This stress the primary importance if its early prevention without iatrogenia by first CaCO3 and vitamin D repletion, as soon as the creatinine clearance decreases below 60 ml/min/1.73 m2.     

Calcium sensing receptor gene polymorphism, circulating calcium concentrations and bone mineral density in healthy adolescent girls

OBJECTIVE: Bone mineral density (BMD) in adolescence is under strong genetic control. The calcium sensing receptor (CASR) is involved in the regulation of calcium homeostasis and bone resorption. The A986S polymorphism of the CASR has recently been associated with serum calcium levels, in one hitherto unconfirmed report. We investigated whether this polymorphism was related to BMD, circulating calcium and parathyroid hormone (PTH) concentrations in girls. DESIGN: BMD, plasma calcium and serum PTH were measured in adolescent girls and compared with regard to CASR genotype. METHODS: In 97 healthy Caucasian girls (mean age 16.9+/-1.2 years (mean+/-s.d.)), the A and S alleles were determined using PCR with a mismatched primer and the restriction enzyme BsaHI. BMD (g/cm) of the total body, humerus, femoral neck and lumbar spine was measured using dual energy X-ray absorptiometry. RESULTS: The genotype frequencies were 71% AA, 26% AS and 3% SS. The genotypes were divided into presence (29%) or absence of S allele (71%). Subjects with the S allele had higher levels of plasma calcium, corrected for albumin (2.17+/-0.06>2.14+/-0.06; P < 0.05, using independent samples t-test), lower BMD at the lumbar spine (P=0.02) and total body (P=0.04), and were significantly less physically active (2.9+/-2.6 vs 4.3+/-2.6 h/week; P=0.01) than the subjects lacking the S allele. PTH levels were not significantly different between the two allelic groups. A multiple regression analysis, including age, height, weight and physical activity, revealed that the CASR allelic variants were not independent predictors of BMD at any site measured (beta=-0.03-0.09; P>0.05). Physical activity was an independent predictor of BMD, was significantly different between the CASR genotypes, and could therefore have a role in explaining the difference in BMD between the CASR genotypes. CONCLUSIONS: The CASR alleles are related to BMD, but it cannot be definitely concluded whether the CASR polymorphism has a direct influence on BMD, or whether the differences in BMD were mediated via an influence of the amount of physical activity.     

Short-term administration of glucagon-like peptide-2. Effects on bone mineral density and markers of bone turnover in short-bowel patients with no colon

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of short-bowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients. METHODS: In an open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years) with small-bowel resection and no colon received 400 microg s.c. of GLP-2 twice daily for 5 weeks. Four received home parenteral nutrition (mean length of residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The outcome measures were the mean percent change from baseline in spinal and hip BMD measured by dual-energy X-ray absorptiometry, changes in four biochemical markers of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of calcium. RESULTS: Mean +/- s(x) (SEM) percent changes in spinal and hip BMD were 1.1+/-0.4% (P < 0.05) and 1.9+/-0.8% (P = 0.06), respectively. The intestinal calcium absorption increased by 2.7% (P = 0.87). Serum ionized calcium increased in 5/8 patients with a concomitant decrease in serum PTH values. Three of the four markers of bone turnover decreased. CONCLUSION: A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.     

Whole body and regional bone mineral density in ankylosing spondylitis

OBJECTIVE: To study the regional distribution of bone mass and look for factors leading to bone loss in ankylosing spondylitis (AS). METHODS: Thirty-nine patients, all men, aged 20 to 55 years and presenting with AS were studied. Four hundred sixteen gendarmes, all men aged 20 to 55 years, formed an age matched control population used to define standard values for bone mineral density (BMD) in men. The patients with AS and the controls underwent measurement of whole body BMD and regional BMD by dual-energy x-ray absorptiometry. RESULTS: AS was associated with spinal bone loss, with lumbar spine BMD (LSBMD) 1.085 +/- 0.178 g/cm2 in the AS group compared with 1.232 +/- 0.136 g/cm2 in the control group (p < 0.01). Whole body BMD and regional BMD of head, whole spine, pelvis, and legs were reduced, although this was not statistically significant. Using standard values for LSBMD from the controls, we found that 46% (18/39) of patients with AS had Z score < -1.5 SD. Biological markers of disease activity were higher in the subgroup of patients with low LSBMD than in the subgroup with normal LSBMD, with an erythrocyte sedimentation rate of 29.4 +/- 23.4 mm/h versus 12.1 +/- 10.8 mm/h (p < 0.05) and C-reactive protein at 24.8 +/- 18 mg/l versus 12.7 +/- 14.2 mg/l (p < 0.05). CONCLUSION: AS is associated with bone loss, mainly concerning the lumbar spine, in patients whose disease is biologically most active.     

Hypocalcemia and parathyroid hormone responsiveness in diabetes mellitus: a tri-sodium-citrate clamp study.

The aim of this study was to elucidate the diabetic hypocalcemia and PTH responsiveness, investigated by measuring blood ionized calcium and serum intact parathyroid hormone (S-PTH(1-84)) concentrations, before and during an induced and maintained controlled hypocalcemia. In 15 patients with insulin-dependent diabetes mellitus and 19 healthy volunteers the blood ionized calcium concentration was lowered by about 0.20 mmol/l and maintained at this level by blood ionized calcium controlled tri-sodium-citrate infusion. In patients vs controls, baseline measurements averaged for blood ionized calcium (mmol/l) 1.18 +/- 0.08 vs 1.24 +/- 0.03 (p less than 0.01), for S-magnesium (mmol/l) 0.73 +/- 0.07 vs 0.81 +/- 0.07 (p less than 0.01) and for S-PTH (1-84) (pmol/l) 3.0 +/- 1.0 vs 3.1 +/- 1.0 (p greater than 0.75). During the clamp, S-PTH (1-84) peaked to comparable maximums after 5-10 min in both groups and then declined to constant concentrations two to three times above their control levels. In conclusion, we found a diabetic hypocalcemia and hypomagnesemia, though baseline levels of PTH and PTH responsiveness were normal. This may be taken to indicate a mild shift downwards in the set-point for PTH secretion in patients with insulin-dependent diabetes mellitus.     

Parathyroid hormone deficiency and excess: similar effects on trabecular bone but differing effects on cortical bone

Parathyroid hormone (PTH) may be anabolic at trabecular bone and catabolic in cortical bone. As many regions of the skeleton contain both types of bone, the effects of PTH deficiency or excess may be difficult to evaluate using bone densitometry, a technique that integrates the cortical and trabecular compartments of bone. We asked the following questions: 1) Is the higher bone mineral density (BMD) in postsurgical hypoparathyroidism due to higher cortical, not trabecular, bone? 2) Is age-related bone loss slowed in patients with postsurgical hypoparathyroidism? 3) Is lower BMD in primary hyperparathyroidism the result of deficits in cortical, not trabecular, bone? BMD of the lumbar spine, proximal femur, distal radius, and femoral midshaft was measured by postero-anterior (PA) scanning, while bone mineral content (BMC) of the third lumbar vertebra was measured by lateral scanning using dual x-ray absorptiometry in 10 women, ages 64.6 +/- 3.2 yr, with postsurgical hypoparathyroidism and in 25 women, ages 68.7 +/- 1.6 yr, with primary hyperparathyroidism. Measurements were repeated 4.7 +/- 0.6 yr later in 8 patients with hypoparathyroidism and 4.0 +/- 0.4 yr later in 20 age-matched controls. Data were expressed as z scores (SD, mean +/- sem) derived from 405 postmenopausal women. In patients with hypoparathyroidism, bone mass z score of the third lumbar vertebra (vertebral body plus posterior processes) was higher than zero by PA scanning (1.26 +/- 0.58 SD, P < 0.05) and lateral scanning (1.04 +/- 0.60 SD, P = 0.1), and higher at the trabecular-rich vertebral body (1.02 +/- 0.47 SD, P = 0.07) and predominantly cortical posterior processes (0.98 +/- 0.66 SD, P = 0.1) determined by lateral scanning. The BMD z scores were higher than zero at the femoral neck (0.89 +/- 0.48 SD, P = 0.09), but not at the femoral midshaft (0.45 +/- 0.60, NS) and distal radius (0.04 +/- 0.51, NS). During follow-up, femoral neck BMD decreased in controls but not in patients with hypoparathyroidism (slope, -0.00818 +/- 0.00496 g/cm2/year vs. 0.00907 +/- 0.00583 g/cm2/year, respectively, P = 0.06). There was no change in lumbar spine BMD in either group. In 25 women with primary hyperparathyroidism, there were no deficits in BMD at the third lumbar vertebra (vertebral body plus posterior processes) by PA or lateral scanning. By lateral scanning, BMC was increased at the vertebral body (0.64 +/- 0.31 SD, P < 0.01) and reduced at the posterior processes (-0.65 +/- 0.26 SD, P < 0.05). BMD was lower at the midshaft of the femur (-0.82 +/- 0.37 SD, P < 0.05) and at the distal radius (-0.68 +/- 0.20 SD, P < 0.01), but not at the femoral neck (-0.08 +/- 0.20 SD, NS). Longitudinal data were unavailable in hyperparathyroid patients. In summary, trabecular bone is increased by both PTH deficiency and excess. Cortical bone loss is slowed by PTH deficiency and accelerated by PTH excess so that suppression of PTH may reduce age-related bone loss and the risk of fracture. Assessment of BMD in PTH deficiency and excess requires the separate study of cortical and trabecular bone.     

Response of alkaline phosphatase to zinc repletion in hypozincemic hemodialysis patients

The response of serum alkaline phosphatase (AP), a zinc-dependent metalloenzyme, to zinc administration via the dialysate (400 micrograms/l) was examined in 14 hypozincemic (less than 30th percentile of dialysis patients) hemodialysis patients and in 14 placebo-treated matched dialysis control patients. Plasma zinc and serum AP were measured three times: prior to, once weekly during (5 weeks), and 2 weeks after addition of zinc to the dialysate. The serum zinc levels remained stable in placebo-treated controls (initial 87.7 +/- 12.5; final 78.6 +/- 8.3 micrograms/dl) and increased in zinc-treated patients (initial 76.4 +/- 8.3; 5th week 96.9 +/- 13.3; 2 weeks after zinc withdrawal 82.3 +/- 12.2 micrograms/dl). There was a slight increase of AP with time in placebo controls (initial 90.2 +/- 26.5; 5th week 100 +/- 29 U/l) and a more pronounced increase in zinc-treated patients (initial 90.8 +/- 19.9; 5th week 113 +/- 20.9 U/l). The difference between the two groups was marginally significant (p less than 0.05; analysis of variance). It is concluded that zinc repletion via dialysate with documented increase of serum zinc levels in initially hypozincemic dialysis patients causes a reversible increase of serum AP. The result is compatible with some tissue zinc deficiency in hypozincemic dialysis patients.     

Altered bone mass and turnover in female patients with adrenal incidentaloma: the effect of subclinical hypercortisolism.

The strategy of treatment for patients with adrenal incidentalomas (AI) may depend upon the presence of hormonal hypersecretion. Although alterations of bone turnover have been recently reported, data on bone mineral density (BMD) are not available in AI patients. We evaluated bone turnover and BMD in 32 female AI patients and 64 matched controls. Spinal and femoral BMD were similar in patients and controls. Serum bone GLA protein (6.8+/-3.5 vs. 8.8+/-3.2 ng/mL; P<0.005) and PTH (48.8+/-15.1 vs. 37.2+/-10.9 pg/mL; P<0.0001) were different in patients and controls. Patients were then subdivided into 2 groups: with (n = 8; group A) or without (n = 24; group B) subclinical hypercortisolism. PTH was higher (P<0.05) in group A than in group B and in both groups than in controls (57.1+/-13.6, 46.0+/-14.8, and 37.2+/-10.9 pg/mL, respectively), and bone GLA protein was lower in group A than in group B and controls (3.8+/-2.3, 7.5+/-3.1, and 8.8+/-3.2 ng/mL, respectively; P<0.05). Serum type I cross-linked C telopeptide and fasting urinary deoxypyridinoline/ creatinine were not different in the three groups. BMD at each site was lower (P<0.05) in group A than in group B and controls. Bone mass and metabolism are altered in AI patients with subclinical hypercortisolism and should be taken into account, therefore, when addressing the treatment of choice for these patients.     

Kinetic of calcium, phosphate, magnesium and PTH variations during hemodiafiltration

Hemodiafiltration (HDF) is a technique resulting from coupling of diffusive and convective transport and thereby increase the elimination of small and middle molecules. However, may induce a convective loss from others substances such as calcium and magnesium. The aim of this study was to evaluate the effects of Ultrafiltration on the kinetics of calcium, phosphate, magnesium and parathyroid hormone. A total of thirteen patients (7 males and 6 females) on hemodialysis, were studied. Each patient was randomly dialyzed with the same dialysate calcium concentration and three different ultrafiltration rate. Schedule A: High flux hemodialysis, schedule B: HDF with 10% of weight body and schedule C: HDF with 20% of weight body. The others parameters were kept identical. Total Ultrafiltration was 2,6+/-0,9 L (9,78+/-3,78 ml/min) in A, 9,3+/-1,7 L (34,54+/-6,22 ml/min) in B and 16,3+/-3,3 L (60,94+/-12,63 ml/min) in C. Replacement fluid during dialysis was 6,85+/-1,42 and 13,65+/-2,9 L. in C and C respectively. Postdialysis total,ionized calcium and magnesium were significantly lower in schedules B and C versus A. PTH levels did not differ significantly. However, PTH changes during dialysis was -36.6+/-38.6%, 6.3+/-69.8% and 32.2+/-63.2% in A, B and C, respectively (p<0.05 A vs. C). A significant inverse correlation was found between total Ultrafiltration and postdialysis levels of total calcium (r:-0.56, p<0.001), ionized calcium (r:-0.65, p<0.001) and magnesium (r:-0.47, p<0.01). No differences were observed in pre and postdialysis phosphate levels, neither mass transfer and clearance of phosphate. We concluded that high ultrafiltration flow rates and substitution fluid without divalent cations induces a negative calcium and magnesium balance. These changes may stimulate PTH secretion during HDF. This technique did not resulted in a higher clearance or phosphate removal.