Aluminum-related bone disease in mild and advanced renal failure: evidence for high prevalence and morbidity and studies on etiology and diagnosis

To study aluminum-related bone disease, bone biopsies and serum biochemical measurements were done in 97 patients on maintenance dialysis and in 100 patients with mild to moderate renal failure. Bone histology, histochemical staining for aluminum and determination of bone aluminum content were done. Stainable bone aluminum was found in 50% of dialyzed patients and in 5% of nondialyzed patients. The finding of stainable bone aluminum in dialyzed patients was associated with high morbidity and mortality; it was not only seen in most patients with low turnover osteomalacia, but also in 47% of patients with mixed uremic osteodystrophy and in 1 patient with predominant hyperparathyroid bone disease. Patients with stainable aluminum had lower bone mass and decreased activity of bone-forming and -resorbing cells. Cumulative doses of aluminum-containing phosphate binders were a major risk factor. Aluminum in drinking water represents an additional risk factor. Neither serum biochemical tests nor single infusion of deferoxamine could be employed as diagnostic tools. Bone biopsies were the only means for diagnosis.     

Clinical and histologic features of iron-related bone disease in dialysis patients

Forty-eight dialysis patients undergoing bone biopsy were analyzed for clinical history, blood biochemical values, bone histologic findings, bone aluminum content (BAC), bone iron content (BIC), bone iron stores, and histochemical staining of bone aluminum and bone iron. Four patients had significant trabecular bone iron staining alone; eight patients had significant bone iron and bone aluminum staining; 13 patients had significant bone aluminum staining alone; and 23 patients showed no significant bone aluminum or iron staining. Patients with significant bone iron staining were younger (37.4 +/- 5.3 years v 53.2 +/- 2.3 years, P less than 0.01, mean +/- SEM) and were more likely to be anephric (P less than 0.001) and to have a history of prior renal transplantation (P less than 0.10). The 12 patients with significant bone iron staining had received more blood transfusions than those without bone iron staining (96 +/- 22.8 U v 22 +/- 5.8 U, P less than 0.005). Patients with bone iron accumulation had higher levels of serum ferritin (3,594 +/- 1,138.4 micrograms/L [ng/mL] v 265 +/- 60.1 micrograms/L, P less than 0.01) and lower levels of immunoreactive parathyroid hormone (iPTH) (349 +/- 150 microLEq/mL v 1,801 +/- 397 microLEq/mL [386 +/- 166 pmol/L v 1,990 +/- 439 pmol/L], P less than 0.005). BIC was also higher in these patients (1,008 +/- 149 micrograms iron/g bone v 300 +/- 46.5 micrograms iron/g bone, P less than 0.001) and higher than normal BIC (256 +/- 44.2 micrograms iron/g bone, eight normals). Bone marrow iron stores were positively related to serum ferritin levels (P less than 0.01) and trabecular bone iron staining (P less than 0.10). All 13 patients with osteomalacia demonstrated significant bone aluminum staining; seven of these patients demonstrated concomitant significant iron staining. Fourteen of 15 patients with severe hyperparathyroidism showed no significant iron or aluminum staining. Our data indicate that iron will probably not accumulate within bone until all other storage sites (eg, bone marrow) are fully saturated. The presence of lower levels of iPTH in iron-overloaded patients raises the possibility that iron overload may induce a state of relative hypoparathyroidism. The most important determinant for the presence of osteomalacia seems to be the presence of significant aluminum staining. No specific bone histologic finding was related to the presence of bone iron staining, but the rarity of isolated significant bone iron staining makes it difficult to evaluate bone histologic diagnoses that might be solely attributable to iron.     

Noninvasive diagnosis of uremic osteodystrophy: uses and limitations

45 bone biopsies from patients with chronic uremia were reviewed to define which noninvasive investigations were of value in predicting the histological diagnosis and to quantify the spectrum of uremic bone disease at a center that has consistently used an aluminum-free dialysis bath. 17 biopsies were taken postmortem. 15 patients received conservative treatment, the rest were on maintenance dialysis. 13 patients had symptomatic bone disease. Virtually all patients with a uremia duration greater than 3 years had uremic osteodystrophy. All patients with clinical bone disease, hypercalcemia or raised alkaline phosphatase activity had osteodystrophy, but the specific histology was not indicated. Greatly raised parathyroid levels suggested secondary hyperparathyroidism, but the test was only 100% specific when 20 times normal. Total aluminum consumption was highly indicative of bone aluminum concentration (p less than 0.0001) and aluminum-related osteomalacia (5 cases), suggesting that a considerable proportion of uremic bone disease is iatrogenic. Serum aluminum was of some use in the diagnosis of aluminum-related osteomalacia, but was not wholly reliable. Bone mineral content (BMC) using both forearm measurements and total body bone mineral levels (TBBM) were assessed in 32 patients and were found to be reduced in 12, with a preponderance of secondary hyperparathyroidism. BMC and TBBM were negatively correlated to resorbing surfaces and bone formation rate, suggesting that secondary hyperparathyroidism is the uremic bone disease that represents the greatest threat to bone mass. It is concluded that while noninvasive investigations give considerable information, reliable diagnosis requires the use of histological methods.     

The effect of high parathyroid hormone levels on the development of aluminum-induced osteomalacia in the rat

A relative deficiency of parathyroid hormone (PTH) is generally observed in dialysis patients with aluminum-associated osteomalacia or aplastic bone disease. It has been suggested that high PTH levels may protect against the development of aluminum-associated bone disease. Through the use of a previously established model of aluminum-induced osteomalacia in the rat, the protective effect of PTH was evaluated. Aluminum was administered intraperitoneally at doses of 0, 5, 10, and 20 mg during a 2-day period, and rats were sacrificed 5 and 12 days after aluminum administration. PTH (bovine 1-34) was administered via a subcutaneously implanted Alzet pump at 2 U/h starting 4 days before aluminum administration and continuing until sacrifice. As the aluminum dose was increased to 20 mg, the osteoblast surface and the bone formation rate decreased. PTH supplementation increased the osteoblast surface at all doses of aluminum and increased the bone formation rate at 0 and 5 mg of aluminum. However, even with PTH supplementation, osteoblast surface decreased as the aluminum dose increased. In the absence of PTH supplementation, osteoblast surface was markedly reduced when the serum aluminum concentration was greater than 400 micrograms/liter or stainable trabecular aluminum surface exceeded 15%. When the stainable trabecular aluminum surface was greater than 12%, the bone formation rate was zero even during supplemental PTH administration. A significant correlation was observed between serum aluminum and stainable trabecular aluminum surface (r = 0.80 at 5 days and r = 0.86 at 12 days; P less than 0.001). However, after PTH administration, less stainable trabecular aluminum was present for the same serum aluminum concentration. Both with and without PTH, the slope of the correlation between serum aluminum and stainable trabecular aluminum surface was steeper at 5 days after aluminum administration than at 12 days. In conclusion, for an equivalent aluminum exposure, high PTH levels protected against the development of low turnover aluminum bone disease in the rat.     

Differential diagnosis between secondary hyperparathyroidism and aluminum intoxication in uremic patients: usefulness of 99mTc-pyrophosphate bone scintigraphy

Forty-one patients in chronic end-stage renal failure and 4 patients with a functioning kidney transplant presented with spontaneous hypercalcemia or intolerance to vitamin D3 sterols and/or oral calcium supplements. Bone iliac crest biopsy with aluminum staining and Tc-pyrophosphate bone scintigraphy with determination of Fogelman score were performed in all cases. Two patients had aluminum-induced osteomalacia (AL O). Thirty-eight biopsies showed renal osteodystrophy (secondary hyperparathyroidism or various combinations of osteitis fibrosa and osteomalacia): 19 with positive staining for aluminum (RO + AL) and 19 without aluminum deposits (RO). The series also comprised 2 cases of pure osteomalacia (OM), 2 cases of osteoporosis (OP), and 1 case of osteoporosis with aluminum accumulation (OP + AL). Mean Fogelman score in RO patients (9.1 +/- 0.3) was significantly higher than in all other categories (5.9 +/- 0.5 for RO + AL, and scores ranging from 0 to 8 in the last 7 patients, p less than 0.01). Patients with massive aluminum accumulation in bone (greater than 75% of the total trabecular surface) showed no or very low uptake of the isotope by the skeleton. Fogelman scores of 9 or higher were always associated with histological secondary hyperparathyroidism. 99mTc-pyrophosphate bone scintigraphy is helpful to distinguish aluminum intoxication from secondary hyperparathyroidism in uremic patients.     

Comparison of bone formation rates measured by radiocalcium kinetics and double-tetracycline labeling in maintenance dialysis patients

We report 23 prospective studies on 18 maintenance dialysis patients in whom we measured skeletal mineralization rate (m) using ⁴⁷Ca, analyzed by the expanding pool model, and compared it with the histologic bone formation rate (bfr), volume referent, estimated on tetracycline-labeled iliac crest bone. The patients showed a spectrum of bone disease types including adynamic bone, aluminum-related osteomalacia, and various degrees of secondary hyperparathyroidism. The mean width between double labels, on which mineral apposition rate depended, was estimated using a simple formula relating area to perimeter for each feature enclosed by the labels. Values for m ranged from 0 to 155 mmol calcium per day and for bfr from 0 to 124% per year. There was close correlation between m and bfr (r=0.976), serum alkaline phosphatase (r=0.968), and serum immunological parathyroid hormone (iPTH) (r=0.868). When the volumetric bfr was converted to mass units and applied to the whole skeleton, using literature values for mineral density and cortical and trabecular mass, there was close agreement between the histologic and isotopic estimates of m (r=0.959). The results validate the two methods and suggest they are interchangeable. However, use of a rigorous method to determine bfr appears to be essential.     

Effects of 1 alpha,25- and 24R,25-dihydroxyvitamin D3 on aluminum-induced rickets in growing uremic rats

Rats were subjected to a two-stage subtotal nephrectomy or sham operation, and treated with aluminum (Al) or both aluminum and vitamin D3 metabolites for 5 weeks with a cumulative dose of 13.6 mg aluminum. Animals were injected with 3H-thymidine and 3H-proline. The following analyses were performed: quantitative histology of tibial metaphyses and cytomorphometric electron microscopy of osteoclasts, quantitative (ICP-spectroscopy) and qualitative determination (histochemical staining) of aluminum within organs, and serum biochemistry (Ca, P, Mg, vitamin D3 metabolites, alkaline phosphatase, urea). The following new facts of the aluminum-related bone disease became evident: (a) Application of aluminum to growing uremic rats induced rickets, whose major epiphyseal growth plate changes were 1 alpha,25(OH)2D3-dependent. Addition of 1 alpha,25(OH)2D3 prevented the formation of rachitic metaphysis, but failed to prevent osteoid accumulation on epiphyseal and metaphyseal trabecular surfaces. Moreover, calcitriol produced hyperosteoidosis and osteosclerosis in the same rats. Aluminum did not alter the function of osteoblasts, while osteoclasts seemed inactivated. (b) The development of rickets was associated with suppressed serum levels of 1,25(OH)2D3, reduced phosphorus level and the high content of aluminum in the bone, kidney, and liver. The addition of 24R,25(OH)2D3 markedly exaggerated the reduction of serum levels of calcitriol. We suggested that aluminum induces rickets in growing uremic rats, which consists of two components: vitamin D refractory osteomalacia and 1 alpha,25(OH)2D3-dependent epiphyseal growth plate changes.     

Renal osteodystrophy in predialysis and hemodialysis patients: comparison of histologic patterns and diagnostic predictivity of intact PTH

BACKGROUND: Comparison of renal osteodystrophy in predialysis and hemodialysis has been rarely reported. Distinct patterns of renal osteodystrophy could be found in these conditions. In addition the use of parathyroid hormone (PTH) and other markers for noninvasive diagnosis may result in different predictive values in predialysis and hemodialysis patients. METHODS: 79 consecutive patients with conservative chronic renal failure and 107 patients on hemodialysis were studied. All patients were subjected to bone biopsy for histological and histomorphometric evaluation. The patients had no exposure to aluminium before dialysis and relatively low exposure while on hemodialysis. RESULTS: In the predialysis patients, bone biopsies showed 9 cases of adynamic bone disease (ABD) and 8 cases of osteomalacia (OM), 50 patients with mixed osteodystrophy and 2 cases of hyperparathyroidism. Among the hemodialysis patients 12 cases had ABD, 3 cases OM, 30 mixed osteodystrophy, and 61 patients hyperparathyroidism. In the predialysis patients with chronic renal failure, bone aluminium was on average 4.5 mg/kg dry weight, while in dialysis patients the average value was 35.4 mg/kg dry weight. Discriminant analysis of low turnover osteodystrophy (ABD and OM) by intact PTH showed higher accuracy in dialysis than in predialysis patients. Correlation studies of intact PTH versus bone formation rate, osteoblast surface/bone surface and osteoclast surface/bone surface showed significantly steeper slopes in dialysis than in predialysis patients, which indicates that bone resistance to PTH is more marked in predialysis patients. CONCLUSIONS: The prevalence of ABD and OM in the geographic area investigated is lower than in other reports. Aluminium exposure does not seem to be the cause of low turnover osteodystrophy in the present population. The predictive value of intact PTH in the noninvasive diagnosis of renal bone disease is higher in hemodialysis patients than in predialysis patients. Predialysis chronic renal failure, when compared to the dialysis stage, seems to be characterized by resistance of bone tissue to PTH.     

Reversal of aluminum-related bone disease after substituting calcium carbonate for aluminum hydroxide

Aluminum-related osteodystrophy, a crippling disease in patients with renal failure, can develop from the long-term ingestion of aluminum hydroxide gels. We present a diabetic patient treated with continuous ambulatory peritoneal dialysis (CAPD) who developed markedly elevated plasma aluminum levels but no musculoskeletal symptoms. Bone biopsy revealed features of the aplastic form of aluminum-related disease with significant aluminum staining, decreased osteoblastic osteoid, and decreased bone formation by double tetracycline labeling, but no excess accumulation of unmineralized osteoid. Aluminum hydroxide gels were discontinued and the patient received calcium carbonate to control hyperphosphatemia; 9 months later, a bone biopsy showed marked improvement of the aluminum-related bone disease, and at 2 to 10 months, plasma aluminum had decreased from 208.7 +/- 10.3 (SE) to 55.7 +/- 3.9 micrograms/L.     

Parathyroid and bone response of the diabetic patient to uremia

Biochemical and radiologic indices of bone disease were assessed in 26 insulin-dependent diabetic patients and 28 nondiabetic patients with endstage kidney disease. The two groups were comparable in age, sex, duration of renal failure, and length of time on dialysis. Diabetic patients showed significantly lower serum calcium and immunoreactive parathyroid hormone (iPTH) levels than nondiabetic patients. iPTH was not related to total serum calcium, but was positively correlated with serum phosphorous (r = 0.37, P less than 0.05 and r = 0.54, P less than 0.005, in nondiabetic and diabetic patients, respectively). iPTH correlated with alkaline phosphatase (r = 0.59, P less than 0.0009) and calcitonin (r = 0.51, P less than 0.05) only in nondiabetic patients. Osteitis fibrosa was noted radiologically in 30% of nondiabetic patients and in none of the diabetic patients (P less than 0.03). Bone morphology in eight diabetic patients who underwent iliac bone biopsy was characterized by reduced trabecular and osteoid bone volume, no woven bone, and marked reduction in indices of bone formation and resorption. The small amount of bone and lack of osteomalacia are a unique feature of the diabetic patient with chronic renal disease. The long-term sequelae of low bone turnover and reduced circulating iPTH may present a special problem to the long term diabetic survivor on the current therapies of uremia.     

Relationships between calcium and phosphorus homeostasis, parathyroid hormone levels, bone aluminum, and bone histomorphometry in patients on maintenance hemodialysis

Serum biochemistry related to calcium and phosphorus homeostasis and parathyroid function was studied together with bone histomorphometry after double-labeling with tetracycline and staining for aluminum in 17 patients without symptoms of bone disease, treated with maintenance hemodialysis for at least 6 months. A close correlation was found between the serum level of parathyroid hormone (PTH) and bone resorption surfaces and bone formation rates, both at tissue and basic multicellular unit (BMU) levels. The patients could be divided into a high turnover group with a normal mineralization process and a low turnover group with markedly defective mineralization. The second group was further characterized by lower PTH and higher fractional aluminum-stained trabecular bone surfaces. For the whole patient material, the fractional aluminum-stained surfaces related inversely to tetracycline-labeled surfaces and to bone formation rates at both BMU and tissue levels, but not to the time on dialysis or to the cumulative ingested amount of aluminum hydroxide. The data provide evidence that PTH or PTH-related factors, besides activating bone remodeling, directly enhance bone formation in dialysis patients and that aluminum incorporation into bone is associated with a progressive disturbance of bone mineralization.     

Cortical v trabecular bone aluminum in dialyzed patients

Differences among measurement of cortical and trabecular bone aluminum (AI) have been observed. Furthermore, its relationship to bone histology has been variable. In order to clarify these points, we have evaluated measurements of bone AI in relation to the source of AI and bone lesion in 25 hemodialysis patients. All patients were dialyzed in the same unit since commencement of dialysis and treated by the same physician. Age of the patients ranged from 29 to 66 years; mean duration of dialysis was 6.6 +/- 3.5 years. Dialysate water has been treated by reverse osmosis since 1980. Bone biopsy was performed in all patients after double tetracycline labeling. AI was measured biochemically in cortical bone (bCAI) and histochemically in trabecular (TAI) and cortical bone (CAI). Mean serum AI (36 +/- 21 micrograms/L) and bCAI (59 +/- 44 micrograms/g) were increased. There were significant correlations between: cortical AI and (1) serum AI (r = 0.71, p less than 0.001); (2) duration of dialysis with softened water (AI content, 55 +/- 21 micrograms/L, r = 0.65, P less than 0.001) but not with total duration of dialysis; and (3) AI ingested since commencement of dialysis (r = 0.57, P less than 0.01). Trabecular AI was not correlated with any of these parameters. None of cortical AI measurements were correlated with bone formation rates (BFR), osteoblastic surfaces (ObS), and resorption surfaces (RS) determined on trabecular bone. However, trabecular AI was inversely correlated with BFR (P less than 0.01) and ObS (P less than 0.05). Serum parathyroid hormone (PTH) was positively correlated with BFR (P less than 0.001) and RS (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Stainable aluminum and not aluminum content reflects bone histology in dialyzed patients

Quantitative evaluation of stainable bone aluminum and measurement of bone aluminum content were done in 55 patients on chronic maintenance dialysis. All patients underwent bone biopsies. Histomorphometry of static and dynamic parameters of bone structure, bone formation and resorption, and quantitation of stainable bone aluminum at the osteoid-bone interface were performed. In addition, bone aluminum content was measured by atomic absorption spectrophotometry. Bone aluminum content was elevated in all patients (81 +/- 9.6 vs. 18 +/- 6 micrograms/g dry wt) and stainable aluminum was found in 47% of them. All patients with predominant low-turnover osteomalacia or adynamic bone disease displayed stainable bone aluminum. In contrast, stainable bone aluminum was not present in individuals with predominant-hyperparathyroid bone disease. Patients with stainable aluminum had lower bone mass (P less than 0.05), higher volume and surface of lamellar osteoid (P less than 0.01), less volume and surface of woven osteoid (P less than 0.05 and P less than 0.01), lower osteoblastic and osteoclastic indices (P less than 0.01), less doubly labelled osteoid seams, lower mineral apposition rate and lower bone formation rates (P less than 0.05 to P less than 0.01). Stainable aluminum correlated with volume of lamellar osteoid and cellular parameters of bone formation and resorption, mineral apposition rate, and bone formation rates (P less than 0.05 to P less than 0.001). In contrast, bone aluminum content correlated with volume of lamellar osteoid only (P less than 0.001). These findings indicate that stainable aluminum at the mineralization front and not aluminum content of bone reflects the histopathologic changes found in bone of dialyzed patients.     

Aluminum alters calcium influx and efflux from bone in vitro

Aluminum retention can cause osteomalacia and adynamic lesions of bone in patients undergoing long-term dialysis. It is not known, however, whether aluminum inhibits the mineralization of bone directly or whether alterations in osteoblastic function mediate this response. To examine this issue, the uptake of 45Ca by 14-day embryonic chick calvaria was measured in vitro. Comparative studies were done in living and devitalized tissues to evaluate the role of bone cells in aluminum-related changes in 45Ca uptake. Aluminum was added to serum-free media as the citrate complex, and paired hemicalvaria maintained in equimolar sodium citrate served as controls. Aluminum citrate decreased the uptake of 45Ca into bone during 24 hour incubations to 76 +/- 3% and 38 +/- 2% (x +/- SD) of control values at 10 microM and 100 microM aluminum, respectively. No change in 45Ca uptake was observed at the end of four hour incubations with 100 microM aluminum citrate, whereas 45Ca uptake decreased from 356 +/- 48 to 266 +/- 36 cpm/micrograms bone, P less than 0.05, at eight hours and from 327 +/- 22 to 269 +/- 41 cpm/micrograms bone, P less than 0.05, at 24 hours. The inhibitory effects of 10 microM and 100 microM aluminum on 45Ca uptake were eliminated, however, in devitalized tissues, and reductions in 45Ca uptake during incubations with aluminum were markedly attenuated by lowering the media phosphorus level from 4.0 mM to 2.0 mM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of parathyroidectomy on aluminum toxicity and azotemic bone disease in the rat

In maintenance dialysis patients, low-turnover osteomalacia and aplastic bone disease are generally attributed to aluminum toxicity. Both groups of patients have a relative deficiency of PTH. The reason for the development of osteomalacia versus aplastic bone disease is unclear. The present study was performed to evaluate whether parathyroidectomy (PTX) modifies the effect of aluminum administration on bone histology in renal failure. Seven groups of pair-fed rats were studied: normals (N); renal failure (RF); RF + PTX; PTX; RF + aluminum (AL); RF + PTX + AL; and PTX + AL. Aluminum was administered intraperitoneally 5 days/week for 6 weeks. All groups were sacrificed at 6 weeks. Renal failure increased the serum calcium in both the parathyroid intact (RF versus N, 11 +/- 0.1 versus 10 +/- 0.3 mg/dl, X +/- SEM, P less than 0.05) and calcium-supplemented PTX groups (PTX + RF versus PTX, 9.7 +/- 0.2 versus 9.2 +/- 0.2 mg/dl, P less than 0.05). After PTX, aluminum administration increased the serum calcium (PTX + AL versus PTX, 9.8 +/- 0.3 versus 9.2 +/- 0.2, P less than 0.05, and PTX + RF + AL versus PTX + RF, 10.8 +/- 0.1 versus 9.7 +/- 0.2 mg/dl, P less than 0.05). In rats with renal failure receiving aluminum, PTX decreased osteoid volume and surface but not osteoid thickness. Rats receiving aluminum did not mineralize bone. Additionally, in PTX rats receiving aluminum, renal failure per se increased osteoblast surface, osteoid surface, osteoid volume, and osteoclast number.(ABSTRACT TRUNCATED AT 250 WORDS)     

Osteomalacia in Fractures of the Proximal Femur

The occurrence of osteomalacia was studied in 58 hip fracture patients who were admitted to the University Central Hospital of Kuopio for operative treatment. Findings indicating osteomalacia were frequent in the series. Hypocalcaemia was found in 70 per cent and an increase in serum alkaline phosphatase in 22 per cent of the patients. Urinary calcium excretion was decreased in 45 per cent and urinary hydroxyproline excretion was increased in 70 per cent of the cases. The serum levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were significantly decreased in the patients compared with the controls. Histomorphometric analysis revealed no difference in the amount of trabecular bone in the patients compared with the controls, but the amount of osteoid and resorption surfaces was increased in the patients. Histological osteomalacia was found in 12 out of 50 patients (24 per cent). In 10 of these 12 cases the diagnosis of osteomalacia was supported by biochemical changes.

There was only one patient, a 29-year-old man with glutein enteropathy who had an evident reason for osteomalacia. The most obvious cause of osteomalacia was the lack of vitamin D due to a deficient diet and lack of exposure to sunlight. The conclusion drawn was that osteoporosis was the main cause and osteomalacia was an important aggravating factor in the bone fragility in these hip fracture patients.     

Studies of bone morphology, bone densitometry and laboratory data in patients on maintenance hemodialysis treatment

Bone morphological parameters of renal osteodystrophy such as abundance of osteoid surface, osteoid seam width index, calcification fronts, osteoclast activity and trabecular bone volume were studied in 71 patients on maintenance hemodialysis and compared with bone densitometry, laboratory and clinical data. Increased osteoclast activity (hyperparathyroidism) was by far the most common bone morphological finding. Patients with chronic pyelonephritis or polycystic kidney disease had more than double the amount of osteoid than patients with chronic glomerulonephritis. The trabecular bone volume seemed to be increased in most patients in contrast to the cortical bone volume which was decreased, judged from bone densitometry and previously from X-ray. Despite that patients with polycystic kidney disease were older, their trabecular volume was larger than in patients with glomerulonephritis. The bone mineral content evaluated by bone densitometry was low in most patients, and more associated with bone morphological signs of osteomalacia than with secondary hyperparathyroidism. Serum phosphate (S-PO4) and serum parathyroid hormone (S-PTH) seemed to discriminate better between osteomalacia and secondary hyperparathyroidism than serum alkaline phosphatase (S-Alk. phosph.), which was elevated in both groups. Patients who had been bilaterally nephrectomized were no more abnormal than other patients, and they had lower S-Alk. phosph. The abundance of osteoclasts was found to be a predictor of future development of clinical secondary hyperparathyroidism.     

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)     

Osteomalacia in Fractures of the Proximal Femur

The occurrence of osteomalacia was studied in 58 hip fracture patients who were admitted to the University Central Hospital of Kuopio for operative treatment. Findings indicating osteomalacia were frequent in the series. Hypocalcaemia was found in 70 per cent and an increase in serum alkaline phosphatase in 22 per cent of the patients. Urinary calcium excretion was decreased in 45 per cent and urinary hydroxyproline excretion was increased in 70 per cent of the cases. The serum levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were significantly decreased in the patients compared with the controls. Histomorphometric analysis revealed no difference in the amount of trabecular bone in the patients compared with the controls, but the amount of osteoid and resorption surfaces was increased in the patients. Histological osteomalacia was found in 12 out of 50 patients (24 per cent). In 10 of these 12 cases the diagnosis of osteomalacia was supported by biochemical changes.

There was only one patient, a 29-year-old man with glutein enteropathy who had an evident reason for osteomalacia. The most obvious cause of osteomalacia was the lack of vitamin D due to a deficient diet and lack of exposure to sunlight. The conclusion drawn was that osteoporosis was the main cause and osteomalacia was an important aggravating factor in the bone fragility in these hip fracture patients.     

Hip fracture incidence not affected by fluoridation. Osteofluorosis studied in Finland

Iliac crest biopsies were taken from patients with hip fracture from a low-fluoride area (less than 0.3 ppm), from an area with fluoridated drinking water (1.0-1.2 ppm), and from a high-fluoride area (greater than 1.5 ppm). Fluoride content analysis and histomorphometry of bone were performed. The hip fracture incidence during 1972-1981 was studied in the same areas. The fluoride content of the bone samples correlated with drinking water fluoride. In patients with hip fracture, both osteomalacia and osteoporosis were common. In the high-fluoride area also osteofluorosis was found in many patients. Osteofluorosis may occur if the fluoride content of trabecular bone exceeds 4,000 ppm and either the volumetric density of osteoid or the osteoid-covered trabecular bone surface is abnormally increased. There was no difference in incidence of hip fracture in the three areas.