Hemodialysis bone disease: correlation between clinical, histologic, and other findings

This paper explores in patients with dialysis osteodystrophy the relationship between clinical features and histological, radiological, and biochemical findings. Eighty-five patients treated by hemodialysis for more than 6 months were studied. The following conclusions were drawn: 1) Bone pain in patients on regular hemodialysis is usually a symptom of developing osteomalacia but not of hyperparathyroidism or osteoporosis. 2) Many patients with histological osteomalacia and radiological features of osteomalacia, such as fractures or Looser zones, have no symptoms. 3)In dialysis patients, biochemical and radiological abnormalities are not a reliable means of predicting the presence of osteomalacia, but a raised serum alkaline phosphatase is a good indicator of the presence of osteitis fibrosa. For early detection of osteomalacia, bone biopsy in necessary. 4)A number of our dialysis patients develop an unusual form of osteomalacia characterized by absent or minimal histological osteitis fibrosa, a normal serum alkaline phosphatase, and a high incidence of myopathy and fractures.     

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis. BACKGROUND: 22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure. METHODS: Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks. RESULTS: Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function. CONCLUSIONS: These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.     

Decreased mineralization in hemodialysis patients after subtotal parathyroidectomy

Summary Many hemodialysis patients undergo subtotal parathyroidectomy (sPTx) because of the complications of severe secondary hyperparathyroidism. In some patients, however, renal osteodystrophy fails to regress. In uremia, the high levels of circulating immunoreactive parathyroid hormone (iPTH) which accompany osteitis fibrosa are associated with accelerated bone formation. After sPTx, the fall in iPTH may decrease mineralization and increase osteoid formation. Bone histomorphometry, densitometry, and serum biochemical determinations were done in 20 patients on regular maintenance hemodialysis and after sPTx in 3 additional patients. Densitometry at the radial diaphysis was inversely related to osteoid volume so that low bone mineral content indicated excess osteoid. Elevated serum alkaline phosphatase activity was associated with osteitis fibrosa. Tetracycline double labels identified 5 patients with an increased rate of mineralization. Levels of iPTH and serum phosphorus were positively correlated to the mineralization rate. The fall in iPTH after sPTx was accompanied by a reduction in osteitis fibrosa and decreased mineralization. The nonosteoblastic osteoid became more abundant. After sPTx some hemodialysis patients may convert the osteitis fibrosa to a poorly treatable low turnover osteomalacia.     

The clinical spectrum of renal osteodystrophy in 57 chronic hemodialysis patients: a correlation between biochemical parameters and bone pathology findings

Fifty-nine chronic hemodialysis patients who had been on dialysis for an average of 77 months underwent bone biopsies and the pathologic findings were correlated with biochemical and demographic data. All but two had evidence of renal osteodystrophy, 23 with osteitis fibrosa (OF), 19 with osteomalacia and/or adynamic disease (OM/AD), and 15 with mixed osteodystrophy (MOD). Patients in each group were similar with regard to age, sex distribution, duration of dialysis, unstimulated serum aluminum, calcium and phosphorus. Patients with osteitis fibrosa (OF) had statistically higher DFO stimulated aluminum, alkaline phosphatase and PTHC levels than the other two groups although there was marked individual variation. The bone biopsies were also evaluated for the amount of aluminum deposited in the osteoid seam. All 23 of the patients with OF and 11 of the 15 patients with MOD had no, mild, or minimal aluminum deposition but 12 of the 19 patients with OM/AD had moderate to marked aluminum deposition. Patients with minimal to mild aluminum deposition were similar in age, duration of dialysis, sex distribution, unstimulated and DFO stimulated aluminum levels, calcium, phosphorus, alkaline phosphatase to those with moderate to marked deposition but had significantly higher parathormone levels. All patients had been treated in a similar fashion regarding diet, oral phosphate binders and vitamin D; therefore, the observed differences in bone pathology were not readily explicable. However, patients who were found to have osteitis fibrosa and those with minimal to mild aluminum deposition had significantly higher parathormone levels when compared with patients in the other groups at the inception of dialysis.     

Which vitamin D derivative to prescribe for renal patients

PURPOSE OF REVIEW: It is possible to control the secondary hyperparathyroidism and osteitis fibrosa of patients with chronic kidney disease by calcitriol when given early and in appropriate doses. However, this control is often achieved at the price of unacceptably high plasma calcium and phosphorus levels, the induction of adynamic bone disease, and soft tissue calcification. To avoid these side effects, so-called 'nonhypercalcemic' vitamin D analogs have been developed. Their possible advantages and their precise place in the treatment and prevention of secondary hyperparathyroidism remain a matter of debate. RECENT FINDINGS: A large US multicenter study showed that the administration of the vitamin D analog paricalcitol to hemodialysis patients, as compared with calcitriol, was associated with better survival. In a subsequent large US multicenter study paricalcitol-treated hemodialysis patients experienced fewer hospitalizations and hospital days compared with calcitriol-treated patients. In a third, smaller study from Japan, regular alfacalcidol users among hemodialysis patients had better cardiovascular survival than nonusers. Finally, in a recent historical control study the mortality of a large hemodialysis patient cohort was analyzed as a function of previous vitamin D treatment. Patients on active vitamin D compounds at any time had a 2-year survival advantage over vitamin D-naive patients. It must be pointed out, however, that all four studies were retrospective in nature. SUMMARY: The development of vitamin D analogs with less side effects than with calcitriol is of major theoretical interest. Practically speaking, however, we still need to be convinced that this goal can be achieved in chronic kidney disease patients.     

Value of the 99mTc-methylene diphosphonate bone scan in renal osteodystrophy

The value of radionuclide bone scanning in the diagnosis of renal osteodystrophy is still debated. In order to re-examine this issue, 25 uremic patients treated by intermittent hemodialysis underwent 99m-Technetium Methylene Diphosphonate (99mTc-MDP) bone scan. They were subdivided into three groups according to quantitative bone histology. Group 1 (N = 8) had pure dialysis osteomalacia, group 2 (N = 7) mixed lesions, and group 3 (N = 10) pure osteitis fibrosa. The scintigraphic studies were interpreted by means of a five point semi-quantitative scale. Using this quantification, all but one group 1 patients had decreased bone tracer uptake, and all patients of group 3 had an increased uptake (chi square test of Yates, P less than 0.001). Among patients of group 2, bone uptake was decreased in the three patients with clearly reduced mineralization front and moderate osteitis fibrosa, but it was increased in all patients with severe osteitis fibrosa and subnormal mineralization front. A quantitative analysis of regional tracer uptake into bone was performed in two patients: one of group 2 and one of group 3. The results obtained clearly corroborated the semi-quantitative findings. Thus, in hemodialysis patients with symptomatic bone disease, the 99mTc-MDP bone scan provides useful information for the differential diagnosis between dialysis-related osteomalacia and secondary hyperparathyroidism. In patients with mixed lesions, the importance of bone tracer uptake appears to depend on the extent of the mineralization front and on the intensity of osteitis fibrosa.     

Skeletal X-ray findings and bone histology in patients on hemodialysis

X-ray films of the hand skeleton (mammography technique), serum chemistry, and quantitative bone histology (micromorphometry of undecalcified sections, iliac crest spongiosa) were compared in 25 patients on maintenance hemodialysis. The X-ray findings correlated better with serum PTH levels than with bone histology. Of all radiological signs of renal osteodystrophy, pronounced subperiosteal resorption (radial aspect, second finger, middle phalanx) and periosteal new bone formation (middle phalanx) correlated best with histological indicators of osteitis fibrosa. These signs were never seen in control patients. Acroosteolysis (endphalanx) and intracortical or endosteal resorption (middle phalanx) were less specific (i.e., seen even in the absence of metabolic bone disease) and correlated less with bone histology. Osteosclerosis in iliac cancellous bone was paralleled by abnormal texture of spongy bone in the proximal metaphysis of the middle phalanx (second finger).     

Elevated bone aluminum and suppressed parathyroid hormone levels in hypercalcemic dialysis patients

We studied 21 dialysis patients who became hypercalcemic without vitamin D or calcium therapy and compared them to 28 dialysis patients who were not hypercalcemic. In the hypercalcemic group, the mean ionized-calcium level was elevated compared to normal subjects (5.4 +/- 0.4 vs. 4.9 +/- 0.1; p less than 0.001), while the ionized-calcium level in the control dialysis patients was below normal (4.5 +/- 0.4 vs. 4.9 +/- 0.1; p less than 0.001). Bone biopsies were performed in all patients. Two thirds of the hypercalcemic patients had low-turnover osteodystrophy (LTO, predominantly osteomalacia), a fraction significantly higher than in the control dialysis patients (13/21 vs. 8/28, respectively; p less than 0.05). The hypercalcemic patients with LTO had markedly elevated surface bone aluminum (63 +/- 24% of all trabecular surfaces). In contrast, the nonhypercalcemic dialysis patients with LTO and all patients with osteitis fibrosa had minimal surface bone aluminum. Hypercalcemic patients with osteitis fibrosa had a significantly lower mean N-terminal parathyroid hormone (PTH) value than did nonhypercalcemic patients with osteitis fibrosa (149 +/- 81 vs. 278 +/- 135 pg/ml, respectively; p less than 0.005). Both mean values were markedly elevated in comparison with those obtained in normal subjects (16 +/- 5 pg/ml). In contrast, patients with LTO, irrespective of the calcium level, had mean PTH values that were not significantly different from those of normal subjects. A PTH level greater than 100 pg/ml was 95% sensitive and 87% specific for osteitis fibrosa, as demonstrated by histomorphometry in nonhypercalcemic dialysis patients. However, this level was only 62% sensitive and 77% specific for a diagnosis of osteitis fibrosa in hypercalcemic dialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal osteodystrophy(II)

Renal bone disease represents one of the major complications of end-stage renal disease, accounting for the numerous and various changes at bone level, determined by abnormal calcium and phosphorus homeostasis and by changes in calcitriol and PTH synthesis. PTH represents as well a major uraemic toxin, exerting profound systemic effects, particularly at the cardiovascular level. PTH synthesis is mainly controlled by changes in calcium-phosphorus balance and calcitriol production by the kidneys. Several others factors are important in the development of secondary hyperparathyroidism: acidosis, autonomisation of PTH secretion and peripheral (target-organ) resistance to PTH actions. Although bone biopsy represents the definitive diagnostic test to differentiate between osteitis fibrosa, low-turnover bone disease and bone involvement unrelated to disturbed calcium metabolism (i.e. beta 2-microglobulin-related amyloidosis), plasma intact PTH generally exhibits a reasonably good relation with bone histology parameters. Moreover serum bone-specific alkaline phosphatase isoenzyme, serum pyridinoline and the novel serum markers for bone turnover are highly specific and correlate with bone histomorphometry parameters, so that, preventive and therapeutic strategies should be re-evaluated based solely on biochemical parameters.     

Renal osteodystrophy (I)

Renal bone disease represents one of the major complications of end-stage renal disease, accounting for the numerous and various changes at bone level, determined by abnormal calcium and phosphorus homeostasis and by changes in calcitriol and PTH synthesis. PTH represents as well a major uraemic toxin, exerting profound systemic effects, particularly at the cardiovascular level. PTH synthesis is mainly controlled by changes in calcium-phosphorus balance and calcitriol production by the kidneys. Several others factors are important in the development of secondary hyperparathyroidism: acidosis, autonomisation of PTH secretion and peripheral (target-organ) resistance to PTH actions. Although bone biopsy represents the definitive diagnostic test to differentiate between osteitis fibrosa, low-turnover bone disease and bone involvement unrelated to disturbed calcium metabolism (i.e. beta 2-microglobulin-related amyloidosis), plasma intact PTH generally exhibits a reasonably good relation with bone histology parameters. Moreover serum bone-specific alkaline phosphatase isoenzyme, serum pyridinoline and the novel serum markers for bone turnover are highly specific and correlate with bone histomorphometry parameters, so that, preventive and therapeutic strategies should be re-evaluated based solely on biochemical parameters.     

Bone growth during daily or intermittent calcitriol treatment during renal failure with advanced secondary hyperparathyroidism

Calcitriol is a standard therapy for secondary hyperparathyroidism in chronic renal failure. We evaluated whether the effect of daily or intermittent calcitriol administration is more efficient in enhancing bone growth in renal failure with advanced secondary hyperparathyroidism in weanling 5/6 nephrectomized rats loaded with phosphorus to induce severe secondary hyperparathyroidism. The animals were treated daily or three times weekly with calcitriol for 4 weeks but the total weekly dose of calcitriol was the same. Although calcitriol increased the serum calcium, it did not lower parathyroid hormone (PTH) or improve tibia and body length. Animals with renal failure and advanced secondary hyperparathyroidism had decreased PTH/PTHrP, which was accompanied by an increase in the cyclin kinase inhibitor p57(Kip2). Calcitriol treatment upregulated the PTH/PTHrP receptor but also increased inhibitors of cell proliferation such as p21(Waf1/Cip1), IGFBP3, and FGFR3. Calcitriol also enhanced markers of chondrocyte differentiation, such as IGF1, Vitamin D receptor, FGF23, and bone morphogenetic protein-7. Receptor activator of nuclear factor-kappabeta ligand levels improved with calcitriol treatment but without changes in osteoprotegerin suggesting an enhancement of osteo/chondroclastogenesis and mineralization. Overall, both daily and intermittent calcitriol had similar effects on endochondral bone growth in phosphorus-loaded rats with renal failure.     

Effect of calcitriol in the control of plasma calcium after parathyroidectomy. A placebo-controlled, double-blind study in chronic hemodialysis patients

Severe, prolonged hypocalcemia in observed in some, but not all, hemodialysis patients after parathyroidectomy performed because of uncontrolled hyperparathyroidism. The aim of the present study was to investigate whether calcitriol and calcium supplementation in the immediate period after parathyroidectomy (days 1-14) was of more help in the control of plasma calcium than calcium supplementation alone. Fourteen hemodialysis patients were enrolled in a prospective, randomized, double-blind and placebo-controlled study. From the day after parathyroidectomy, 7 patients received calcitriol and the remaining 7 a placebo using incremental doses adjusted to the degree of hypocalcemia (up to 4 micrograms/day for calcitriol). Plasma calcium, phosphorus, alkaline phosphatase and immunoreactive parathyroid hormone levels before parathyroidectomy were comparable in both patients groups, as was the lowest plasma calcium achieved after parathyroidectomy. The decrease in plasma calcium after parathyroidectomy was related to plasma alkaline phosphatase and to the number of osteoclasts and osteoblasts on bone biopsy surface before parathyroidectomy. The mean decrement of plasma calcium (days 3-9) as compared to that before parathyroidectomy was less pronounced in calcitriol-treated than in placebo-treated patients (0.25 +/- 0.06 versus 0.45 +/- 0.05 mM, mean +/- SEM, p less than 0.025). Treatment with placebo was interrupted before day 14 because of persistent severe hypocalcemia in 4 of 7 patients, whereas calcitriol treatment was continued in all 7 patients up to 14 days. Patients on calcitriol treatment required less mean calcium supplements (days 1-9) than patients receiving placebo (37.4 +/- 3.2 versus 49.4 +/- 3.7 g, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double-blind study among 4 doses

BACKGROUND/AIMS: Although the PTH-suppressive effect of intravenous calcitriol has already been demonstrated by various studies, the precise dose-response to calcitriol has not been fully determined for uremic secondary hyperparathyroidism (2HPT). In order to investigate in detail the dose-response of intravenous calcitriol and the adequate initial dose against 2HPT, a randomized prospective double-blind study was conducted. METHOD: One-hundred and sixty-two patients with 2HPT undergoing hemodialysis three times per week were randomly assigned to four calcitriol (Ro21-5535) treatment groups, 0 (placebo), 1, 1.5 or 2 microg. Calcitriol or placebo was given intravenously after each dialysis for 12 weeks under double-blind conditions. RESULTS: Calcitriol dose-dependently reduced both intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels. The rate of per-week change in intact-PTH was 0.0% in the placebo group, -7.8% in the 1-microg group, -18.9% in the 1.5-microg group and -24.1% in the 2-microg group. Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted by albumin level. The per-week increases in adjusted serum Ca were -0.01, 0.08, 0.23 and 0.35 mg/dl in the placebo, 1-, 1.5- and 2-microg groups, respectively. Although the degree of PTH suppression was correlated with the adjusted serum Ca increase, by-patients investigation revealed that the number of patients with suppression of PTH despite of no or slight elevation of adjusted serum Ca level was largest in the 1-microg group among the three calcitriol groups. CONCLUSION: Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT, and the appropriate initial dose of this agent was determined to be 1 microg per dialysis session.     

Ketodiet, physiological calcium intake and native vitamin D improve renal osteodystrophy.

The effects of a very low-protein diet (VLPD) supplemented with amino acids and ketoanalogues (KA) and with 1 g of calcium carbonate and 1000 IU of vitamin D2, were studied in 17 patients with advanced renal failure (GFR < or = 20 ml/min) over a period of one year. The protein intake was 0.3 g protein/kg body wt/day. Daily phosphorus and calcium intake were respectively 1,500 mg and 300 mg. Sequential bone densitometry was performed and bone histomorphometry after double tetracycline labeling was evaluated, before and after one year of diet. Calcium and phosphate metabolism parameters were monitored every two months. In spite of a significant decrease of GFR, phosphorus, parathyroid hormone (1-84) and osteocalcin plasma levels decreased significantly, while low plasma bicarbonate normalized, and calcitriol and calcium levels remained respectively low and normal. Before the diet, histological study disclosed four cases of mixed osteopathy: osteomalacia associated with osteitis fibrosa (OM/OF), nine pure osteitis fibrosa (OF) and four with normal bone remodeling (NB). After one year of diet, the OM component of OM/OF disappeared, as evidenced by a normalization of the mineral apposition rate and osteoid thickness. In the patients presenting pure OF, a significant decrease in osteoblastic and osteoclastic surfaces, in the number of osteoclasts, and in the bone formation rate (BFR) were found. Vertebral mineral density measured by quantitative computerized tomodensitometry did not change significantly. In conclusion, this study not only confirms the beneficial effects of VLPD + KA + calcium on uremic hyperparathyroid bone disease in advanced renal failure assessed using static bone histomorphometry, but also shows a correction of histodynamic bone parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of chronic intravenous calcitriol on parathyroid function and set point of calcium in dialysis patients with refractory secondary hyperparathyroidism.

This study evaluates the effect of intravenous calcitriol on parathyroid function and ionized calcium-PTH sigmoidal curve obtained during low- and high-calcium haemodialysis in 10 patients with osteitis fibrosa whose secondary hyperparathyroidism was refractory to conventional therapy. After 4 months of intravenous calcitriol, serum ionized calcium increased from 1.28 +/- 0.08 to 1.37 +/- 0.11 mmol/l (P less than 0.001), serum phosphate from 1.54 +/- 0.18 to 1.79 +/- 0.4 mmol/l (P NS), serum calcitriol from 16.7 +/- 9.9 to 34.3 +/- 6.4 pg/ml (P less than 0.001), while alkaline phosphatase decreased from 366 +/- 340 to 226 +/- 180 IU/l (P less than 0.05), osteocalcin from 46.4 +/- 20 to 34.5 +/- 15.3 ng/ml (P less than 0.05), and basal intact PTH from 1069 +/- 700 to 305 +/- 270 (P less than 0.01). Basal PTH started to decrease after 1 month of treatment prior to the increase in the ionized calcium. Because of hypercalcaemia the dialysate calcium was decreased from 1.75 to 1.5 mmol/l in three of five patients on haemodialysis, and calcium-containing solutions were replaced by calcium-free fluids in four of five patients on haemodiafiltration. Calcitriol dose, at the first month of therapy was 5.6 +/- 0.8 micrograms/week, but it was successively decreased because of hypercalcaemia to a final dose of 3.6 +/- 1.3 micrograms/week. After intravenous calcitriol the ionized calcium-PTH sigmoidal curve shifted to the left and downward. Maximally stimulated PTH and maximally inhibited PTH obtained during low- and high-calcium dialysis significantly decreased, as well as the ratio of basal PTH/PTHmax and the set point of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parathyroid hormone and bone histology: response to hypocalcemia in osteitis fibrosa

The parathyroid hormone (PTH) response to hypocalcemia was studied in 18 hemodialysis patients with osteitis fibrosa, and the relationship with PTH and bone histology in 26 hemodialysis patients. Hypocalcemia was produced during hemodialysis by the use of a dialysate devoid of calcium. Both amino (N) (P less than 0.05) and carboxy (C) (P less than 0.005) terminal PTH attained maximum levels by 15 min despite only a minimal decline in plasma calcium. Throughout the remainder of the study, C and N-PTH levels remained elevated but did not increase despite a further decline in plasma calcium. Five patients increased both C and N-PTH to maximum or near maximum levels by the first sampling, although plasma calcium remained above 9 mg/dl. Basal C and N-PTH correlated with the maximum levels of each induced by hypocalcemia (P less than 0.005). Both basal N-PTH and the maximum change in C-PTH produced by hypocalcemia correlated with osteoblastic osteoid, active resorption, osteoclasts/mm2, and endosteal fibrosis (P less than 0.005). In conclusion, (1) a minimal decline in plasma calcium produces a maximum C and N-PTH response; (2) an altered PTH set point may be present in some hemodialysis patients; (3) the correlation between basal and maximally stimulated PTH levels suggests that basal PTH levels may reflect parathyroid gland mass; and (4) a correlation with basal and stimulated PTH and bone histology is present.     

Dose-response effect of short-term calcitriol treatment on bone and mineral metabolism in normal males

To evaluate the effects of short-term treatment with calcitriol on biochemical markers of calcium and bone metabolism, 36 normal male volunteers (aged 21–54 years) were randomized to oral treatment for 7 days with either (A) calcitriol, 1 μg twice daily, (B) calcitrol, 0.5 μg twice daily, or (C) placebo twice daily. Serum calcium increased slightly in a dose-dependent manner (maximal increase 2.5%, p < 0.05) followed by a heavy increase in both 24 h (max. 156.1%, p < 0.001) and fasting urinary calcium excretion (max. 123.1%, p < 0.001), and a striking reduction in serum PTH (max. −43.1%, p < 0.001). Biochemical markers of osteoblast activity and bone formation increased immediately in a dose-dependent manner [serum osteocalcin (max. 37.8%, p < 0.03) and serum procollagen type I C-terminal propeptide (PICP) (max. 26.0%, p < 0.05)], whereas there was no effect on serum bone alkaline phosphatase. Calcitriol treatment had no effect on biochemical markers of bone resorption [serum C-terminal telopeptide of type I collagen (ICTP) and fasting urinary excretion of hydroxyproline/creatinine (OHP)]. Extraosseous collagen matrix synthesis was not affected evaluated by serum procollagen type III N-terminal propeptide (PIIINP). In the follow-up period (15 weeks) no unequivocal changes were observed. The fast and protracted increase in biochemical markers of osteoblast activity and bone formation, without affecting bone resorption and extraosseous connective tissue metabolism points toward a selective effect of calcitriol on bone matrix formation.     

Bone histomorphometry is still the golden standard for diagnosing renal osteodystrophy

AIM: The clinical picture of renal osteodystrophy (RO) is very uncharacteristic. The diagnosis is made by means of biochemical indicators, intact parathormone (iPTH) concentration, bone X-rays, bone densitometry and particularly bone histomorphometry. The aim of our study was to establish whether a combination of non-invasive methods can bring us closer to the diagnosis as to avoid bone biopsy. PATIENTS AND METHODS: We chose 30 patients treated by chronic hemodialysis. Only 4 of them had no symptoms of RO. Biochemical parameters (Ca, P) and iPTH concentrations were determined. bone X-rays were taken (the parathyroid series), bone mineral density was measured by quantitative digital radiography (QDR), and bone biopsy specimens were taken for bone histomorphometry. The data were analyzed by the Statistica by StatSoft and SPSS computer programs. RESULTS: With respect to bone histomorphometry, 10 patients had osteitis fibrosa (OF), 15 had mixed osteodystrophy (MO), 5 adynamic bone disease (ABD). There was a good correlation of iPTH and alkaline phosphatase (AP) concentrations with histomorphometric parameters. There was also a correlation between radiological changes and histomorphometric parameters. After the analysis of discrimination using the SPSS computer program, taking only iPTH into consideration, 36.6% of patients were correctly classified according to their diagnosis. Considering iPTH and densitometry, 46.6% were classified correctly. Considering iPTH and radiological changes, 60% of patients were classified correctly. CONCLUSION: To diagnose 73.3% of patients correctly, it was necessary to consider the above mentioned non-invasive parameters, as well as AP, P, concentrations and the patient age. Histomorphometry remains the "golden standard" for diagnosing RO.     

Parathyroid hormone response to hypocalcemia in hemodialysis patients with osteomalacia

The parathyroid hormone response to hypocalcemia was investigated in hemodialysis patients with osteomalacia and compared to those with osteitis fibrosa. Hypocalcemia was induced during hemodialysis by employing a dialysate devoid of calcium. Patients with osteomalacia had a blunted maximum amino terminal parathyroid hormone response (+/- SD) (0.39 +/- 0.33 vs. 0.87 +/- 0.53 ng/ml, P less than 0.05) and maximum carboxy terminal parathyroid hormone response (+/- SD) (0.36 +/- 0.20 vs. 0.84 +/- 0.47, P less than 0.02) to hypocalcemia. The decline in plasma calcium was greater in patients with osteomalacia at 90 (P less than 0.05), 120 (P less than 0.01), and 150 min (P less than 0.01). In osteomalacia patients the surface density of histologically detectable trabecular bone aluminum correlated directly with the percent relative osteoid volume (P less than 0.005) and inversely with the maximum amino terminal parathyroid hormone response to hypocalcemia (P less than 0.025). These results suggest that hemodialysis patients with osteomalacia have diminished secretion of parathyroid hormone and a decreased ability to restore plasma calcium homeostasis during hypocalcemia.