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Fine needle aspiration cytology of central giant cell granuloma of the jaw. A report of two cases.

Two patients with recurrent central giant cell granuloma (CGCG) who underwent fine needle aspiration biopsy are reported. This lesion has a distinct clinicoradiologic profile and occurs almost exclusively in the mandible and/or maxilla of young individuals. The essential cytologic findings included a dual cell population consisting of mononuclear stromal cells and multinucleate giant cells. These features were considered not specific for the diagnosis of CGCG and are identical to those of osteitis fibrosa cystica and giant cell tumor of bone. If the features are taken together with the clinical, radiologic and laboratory data, the diagnosis of CGCG is possible. The utility of osseous fine needle aspiration biopsy and the clinical, radiologic and cytologic findings of bone lesions containing giant cells are discussed.

Biopsy, Needle↗

1 alpha-hydroxycholecalciferol in hemodialysis renal osteodystrophy. Adverse effects of anticonvulsant therapy.

Two regular hemodialysis patients were assessed before, during and after therapy for 8 1/2 months with 1alpha-hydroxycholecalciferol (1alphaOHD3). The first patient (F.S.), treated with 2 mug daily, improved considerably with complete resolution of histological osteomalacia (O.M.), reduction in osteitis fibrosa (O.F.) and healing of Looser zones. The second patient (T.Y.), who was treated at the same time with a combination of phenobarbitone and phenytoin, showed no improvement while taking 3 mug of 1alphaOHD3 daily. It is suggested that hepatic microsomal enzyme inducing drugs antagonize the action of 1alphaOHD3 by interfering with its subsequent hepatic 25-hydroxylation.

Alkaline Phosphatase↗

Improvement of secondary hyperparathyroidism and reduction of the set point of calcium after intravenous calcitriol.

In this study we evaluated the effect of intravenous calcitriol on parathyroid function and ionized calcium/PTH sigmoidal curve obtained during low and high calcium hemodialysis in 10 patients with osteitis fibrosa whose secondary hyperparathyroidism was refractory to conventional therapy. After four months of intravenous calcitriol, serum ionized calcium increased from 1.28 +/- 0.08 to 1.37 +/- 0.11 mmol/liter (P < 0.001), serum phosphate from 1.54 +/- 0.18 to 1.79 +/- 0.4 mmol/liter (P = NS), serum calcitriol from 16.7 +/- 9.9 to 34.3 +/- 6.4 pg/ml (P < 0.001), while alkaline phosphatase decreased from 366 +/- 340 to 226 +/- 180 IU/liter (P < 0.05), osteocalcin from 46.4 +/- 20 to 34.5 +/- 15.3 ng/ml (P < 0.05) and basal intact PTH from 1069 +/- 700 to 305 +/- 270 (P < 0.01). Basal PTH started to decrease after one month of treatment prior to the increase in the ionized calcium. Because of hypercalcemia, the dialysate calcium was decreased from 1.75 to 1.5 mmol/liter in three of five patients on hemodialysis and calcium-containing solutions were substituted by calcium-free replacement fluids in four of five patients on hemodiafiltration. Calcitriol dose at the first month of therapy was 5.6 +/- 0.8 micrograms/week, but successively it was decreased because of hypercalcemia 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 did the ratio of basal PTH/PTHmax and the set point of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗

Parathyroid adenoma in northern Nigeria.

A middle-aged farmer and a female student presented with osteitis fibrosa cystica with nephrocalcinosis in the former and nephrolithiasis in the latter due to primary hyperparathyroidism. Hypercalcaemia was present in both cases and neck exploration revealed a large solitary parathyroid adenoma which was excised. Because primary hyperparathyroidism is less common in tropical countries doctors may be less familiar with the early manifestations of the disease. The number of patients thus undiagnosed and untreated is unknown.

Adenoma↗

The relevance of mineralization lag time in the evaluation of histologic changes in renal osteodystrophy.

We examined bone biopsies from 47 patients on chronic hemodialysis, and analyzed the histomorphometric and biochemical findings and histologic quantitation of bone aluminium, looking primarily at mineralization lag time (Mlt) to evaluate its usefulness in categorization of renal osteodystrophy (ROD). The patients were categorized as having either relatively normal Mlt (< 35 days, n = 21 patients), moderately prolonged Mlt (35-100 days, n = 13 patients) or markedly prolonged Mlt (> 100 days, n = 13 patients). The group with relatively normal Mlt showed significantly higher C-terminal parathyroid hormone (PTHc) levels (26,141 +/- 19,270 vs 7,226 +/- 6,073 and 4,434 +/- 4,000 pg/ml) than the moderately or markedly prolonged Mlt groups (p < .01) and was associated with histologic characteristics of osteitis fibrosa or mild hyperparathyroidism (BFR/BS range 0.146-0.947 mcm3/mcm2/d). The group with markedly prolonged Mlt included one patient with classic and 11 with adynamic osteomalacia (BFR/BS range 0.009-0.099) and had greater bone aluminum (Al.S/OS 35.3 +/- 26.7% vs 7.2 +/- 9.0%) than the normal Mlt group (p < .01). The group with moderately prolonged Mlt included two patients with aplastic bone disease (Mlt 80.0 and 84.6 days, and Al.S/OS 100.0 and 72.3%) and 11 patients with features of hyperparathyroidism and osteomalacia (BFR/BS range 0.068-0.243) with variable but generally intermediate bone aluminum deposition (Al.S/OS 22.5 +/- 19.9%). Like BFR/BS and other dynamic parameters Mlt correlates with morphologic types of ROD which primarily reflect bone turnover, but it may also suggest varying degrees of mineralization impairment in a spectrum ranging from high to low turnover types of ROD. Its usefulness in this respect should not be overlooked.

Bone Density↗

Type I procollagen propeptide in patients on CAPD: its relationships with bone histology, osteocalcin, and parathyroid hormone.

Serum procollagen type I carboxyterminal propeptide (PICP) has been shown to be a useful marker of bone formation in patients undergoing haemodialysis. However, PICP levels has not been evaluated in depth in patients maintained on continuous ambulatory peritoneal dialysis (CAPD). Therefore serum and dialysate levels of PICP, its peritoneal clearance (Clp), mass transfer (MTp), and its possible relationship with osteocalcin, parathyroid hormone (PTH), and bone histomorphometry were studied in a group of CAPD patients. Serum PICP was just above the normal range with significant amounts detected in the dialysate but no correlations were found between levels of serum PICP, dialysate PICP, and Clp-PICP. One patient with systemic lupus and osteitis fibrosa had extraordinarily high serum and dialysate levels of PICP. The patient later developed sclerosing peritonitis. No associations were seen between serum PICP and Clp-PICP and any of the 18 bone histomorphometric parameters evaluated. Dialysate level of PICP correlated negatively with mineral appositional rate (r = -0.62, P < 0.01) and mineralization lag time (r = 0.64, P < 0.01). MTp-PICP correlated positively with mineral appositional rate (r = 0.65, P < 0.01). Serum osteocalcin and serum PTH levels did not correlate to serum, dialysate, Clp or MTp measurements of PICP. These results suggest that measurements of PICP in CAPD patients do not give substantial information as an non-invasive marker of bone histology.

Adult↗

Silent and progressing accumulation of aluminum in bone without definite histological osteomalacic aspects in chronic hemodialysis patients.

The aluminum (Al) contents of the tap water and the dialysis fluid in our center had proven to be less than 10 micrograms/l during more than 10 years. We evaluated the Al content, stainable Al, and the histomorphometry of the bone biopsy specimens from the 23 chronic renal failure patients on dialysis. The plasma Ca, P, Mg, ALP, C-PTH, and Al levels except calcitonin (CT, r = 0.442, p < 0.05) had no significant relationship to the hemodialysis (HD) duration. Their bone histologies were classified as osteitis fibrosa (OF) in 9, mild type (MILD) in 11, mixed type (MIXED) in 2, and osteomalacia (OM) in 1. The stainable Al% on the trabecular bone surface showed a positive correlation with HD duration (r = 0.569, p < 0.001), with the bone Al content (r = 0.455, p < 0.05), and with the bone Al/Ca ratio (r = 0.668, p < 0.01), respectively. The bone Al, Ca and Mg content did not correlated with HD duration and with plasma Al levels, although the bone Al/Ca ratio showed a strong correlation with HD duration (r = 0.675, p < 0.01) and with plasma Al levels (r = 0.719, p < 0.001). In the histomorphometric parameters, plasma Al levels, stainable Al, bone Al content, as well as bone Al/Ca ratio had no significant correlation with the osteomalacic aspects. Thus, our observations revealed that the Al accumulation in the bones was latent and progressing without definite osteomalacic changes, even though the dialysate Al concentration was under the critical level. Other Al invasion roots besides dialysis fluid should be regarded, including oral intake of Al-containing phosphate binders or other gastrointestinal medicines, as well as food content.

Aluminum↗

[Correlation between osteocalcin and bone histomorphometry in children with chronic renal failure].

The study was performed in 17 children with chronic renal failure, 7 were on hemodialysis, 6 on continuous ambulatory peritoneal dialysis, 4 were treated conservatively. In all, serum levels of alkaline phosphatase, PTH intact and osteocalcin were measured and bone biopsy was performed. We analyzed correlations between biochemical markers of bone metabolism and histomorphometric parameters. The lowest mean serum osteocalcin levels were found in children with adynamic bone disease, the highest with osteitis fibrosa. The serum osteocalcin level was significantly correlated with the dynamic parameter of bone formation rate (BFR), which suggests that this biochemical marker can be of use in discriminating between renal osteopathy with low and high bone turnover. Lack of correlation between serum osteocalcin level and mineralizing surface confirms it significance as a good marker of osteoblastic activity in bone formation but not in bone mineralization.

Alkaline Phosphatase↗

The influence of growth hormone treatment on bone metabolism in dialysis patients.

Bone formation markers, PTH intact, and bone mineral density were evaluated in 12 children with end stage renal disease during recombinant human growth hormone (rhGH) treatment. Bone biopsies before rhGH therapy revealed: osteitis fibrosa in one patient, mild lesions in eight, adynamic bone disease in one, and a normal histology in two. PTH intact increased after six months of rhGH in seven children, and was significantly higher in them than in the control group. A positive correlation between PICP concentration after one month and growth velocity within 12 months of rhGH was found. Higher doses of vitamin D are needed in growing children treated with rhGH.

Adolescent↗

Treatment of bone disease with dihydrotachysterol in patients undergoing long-term hemodialysis.

Nine of 24 patients undergoing long-term hemodialysis were found to have evidence of moderate to severe bone disease. Two had bone pain and muscle weakness and two had pseudofractures. Eight of the nine were treated with dihydrotachysterol (DHT), 0.25 to 0.375 mg/d initially, but four required doses between 0.5 and 1.0 mg/d. Ther serum alkaline phosphatase value decreased in all patients and returned to normal in six. The bone pain and muscle weakness resolved and the pseudofractures healed. Bone biopsies in six patients before and after initiation of treatment with DHT showed that the osteoid area decreased significantly from 29.6 +/- 22.8% (mean +/- standard deviation) to 11.5 +/- 7.5% (P less than 0.025) and the resorptive surface decreased in all patients. DHT, in doses of up to 1.0 mg/d, is effective in treating both the osteitis fibrosa and the osteomalacic components of bone disease in patients undergoing hemodialysis.

Bone and Bones↗

[Relative depletion in native vitamin D: a potential risk factor in Algerian hemodialysis patients with radiological evidence of hyperparathyroidism and osteomalacia independent of calcitriolemia].

Looser striae on the ischio-pubian branches and subperiosteal resorption of the phalanges were looked for in 113 chronic hemodialysis patients at the University Hospital of Annaba (Algeria) and were found in respectively 14 and 48 patients. Comparison of patients with and without radiological complications showed no significant difference in their age, sex ratio, nature of initial kidney disease and duration on dialysis. The patients with Looser striae had lower plasma levels of 25OHD3 than those without striae, whereas all other plasma parameters were similar. The plasma concentrations of intact PTH were higher in patients with resorption; these patients had lower plasma concentrations of calcium, bicarbonate, aluminum and 25OHD3 but similar plasma concentrations of phosphate and 1,25(OH)2D3. Multivariate analysis showed that PTH concentrations were independently linked only to plasma 25OHD3 (negatively) and duration on dialysis (positively). The results of this transversal study are in agreement with the well established pathophysiological roles of PTH hypersecretion, hypocalcemia and acidosis in the appearance of radiological hyperparathyroidism in hemodialysis patients. Furthermore they suggest that a relative native vitamin D deficiency may have a calcitriol independent role in favoring the occurrence of both osteitis fibrosa and osteomalacia.

Adult↗

Calcifediol in chronic renal insufficiency. Skeletal response.

Quantitative histology of thin, nondecalcified sections was performed on sequential bone biopsy specimens from five patients undergoing long-term hemodialysis and treated with calcifediol (25-hydroxycholecalciferol) for periods of three to nine months. With increase of intestinal absorption of calcium and decline of circulating immunoreactive parathyroid hormone and alkaline phosphatase, the bones of each patient exhibited striking histological improvement. The group as a whole showed statistically significant decreases in osteoclast number and in the percentages of osteoid surface covered by active osteoblasts. Marrow fibrosis was either eliminated or strikingly decreased in each patient. Osteoid volume significantly declined in four of five patients. In patients with osteitis fibrosa as the predominant histological lesion, calcifediol therapy resulted in decreased calcification front activity. Increased activity was the result when osteomalacia predominated.

Adult↗

Treatment of bone disease in patients on chronic hemodialysis with dihydrotachysterol.

Nine out of 24 patients on chronic hemodialysis were found to have biochemical, radiologic and bone biopsy evidence of moderate to severe bone disease. Two patients had bone pain and muscle weakness, 2 had pseudofractures, and one patient had a pathologic fracture of the neck of the femur. Eight patients were treated with dihydrotachysterol (D.H.T.), 0.25 to 0.37 mg/day initially. Four patients required doses between 0.5 and 1.0 mg daily. The alkaline phosphatase decreased in all patients, returning to normal in 6 patients. The symptoms of bone pain and muscle weakness resolved, and the pseudofractures healed. Repeat bone biopsies were performed in 6 patients 12 mos or more after treatment with D.H.T. The osteoid area fell from 29.6 +/- 22.8 to 11.5 +/- 7.5% (p less than 0.025). Resorptive surface decreased in all patients. D.H.T., in doses of up to 1.0 mg/day, is effective in the treatment of both the osteitis fibrosa and the osteomalacic component of bone disease in patients on hemodialysis.

Calcium↗

Geriatric primary hyperparathyroidism.

Primary hyperparathyroidism occurs in a significant number of patients over 60 years of age; about one-third of the 182 patients we studied were in this age group. Primary hyperparathyroidism has been recognized with greater frequency in recent years, particularly in patients without manifestations of renal lithiasis or osteitis fibrosa cystica and in older patients. Age alone is not critical in the occurrence of serious complications from hypercalcemia, the presence of other life-endangering disease, or the development of major postoperative complications in the management of primary hyperparathyroidism. A liberal but selective policy is advocated in advising operation for primary hyperparathyroidism in the elderly. Different clinical patterns of primary hyperparathyroidism are recognized in all age groups. The operative procedure for primary hyperparathyroidism is determined primarily by the surgeons at the time of operation, on the basis of gross characteristics of the parathyroid glands. A precise correlation is not found between microscopic changes, gross changes, and clinical features of primary hyperparathyroidism.

Aged↗

Reversal of the histology of bone after parathyroidectomy in patients with hyperparathyroidism.

Hyperparathyroidism is commonly seen in patients with end-stage renal disease and less commonly in the primary form. The skeletal manifestations of hyperparathyroidism are the same in both forms and are well described in the literature. We treated a patient from each category. Multiple bony lesions and pathologic fractures were observed. The clinical presentations and radiologic and histologic findings confirmed the diagnosis of hyperparathyroidism and osteitis fibrosa cystica in both patients. Subtotal excisions of the parathyroid glands were done in both patients. Appropriate treatment of the bony lesions and pathologic fractures resulted in healing. Histologic evaluation of the bony lesions indicated an osteoblastic or healing response. The reversal of the histologic pattern in just 5 days and 16 days after parathyroidectomy was noted. In treating such patients, physicians should consider parathyroidectomy as an aid in the overall management of patients.

Adult↗

Case of the month: March 1998--48 year old man with back pain and weakness.

A 48 year old man with long history of end stage renal disease (ESRD) and secondary hyperparathyroidism presented with back pain and incontinence. MRI and CT showed T2 expansion with bony destruction and spinal cord compression. Other vertebral bodies showed destructive lesions as well. Microscopic examination showed a brown tumor composed of multinucleated giant cells and bone uninvolved by tumor showed "tunneling" resorption. Brown tumors are an exaggerated form of "local" osteitis fibrosa cystica in patients with ESRD and secondary hyperparathyroidism, but spinal cord compression is rare.

Back Pain↗

[Anomalies of phosphate and calcium metabolism in chronic renal insufficiency].

The disturbances of calcium and phosphate metabolism in chronic renal failure involve mainly two hormones, namely calcitriol and parathyroid hormone. They are thought to start with a reduction in calcitriol synthesis, probably due to several mechanisms, and with a reduced action of calcitriol at its target tissues, including the parathyroid cell. They may lead to several complications of clinical importance including both secondary hyperparathyroidism, in the presence or absence of vitamin D deficiency, and hypoparathyroidism. The corresponding expression at the bone level may be osteitis fibrosa, osteomalacia or adynamic bone disease. These complications are frequently associated with soft tissue calcifications, mainly vascular and periarticular, with serious clinical consequences in some patients.

Bone Diseases↗

A patient of primary hyperparathyroidism with full-blown bone changes simulating malignancy.

The two most common causes of hypercalcemia are malignancy and primary hyperparathyroidism (1 degree HPT). The radiographic presentations and the histological findings on bone biopsy are important for differential diagnosis of underlying diseases. We report a patient with hypercalcemia who presented unusual bone manifestations. A 43 y/o woman was admitted due to right femoral fracture. X-ray on the right tibia revealed several osteolytic cystic lesions with sclerotic rims. Blood biochemistry showed anemia, impaired renal function and hypercalcemia. Multiple osteolytic lesions on the skull and bilateral forearms were also noted. Malignancy, such as multiple myeloma or metastatic cancer was suspected. However, this was excluded because of the absence of M-component on serum protein electrophoresis and the negative finding of plasma cells or other malignant cell on bone biopsy examination. Abdominal sonography demonstrated bilateral medullary nephrocalcinosis. The final diagnosis of 1 degree HPT was made, based on the findings of classic pathological pictures (brown tumor) and the markedly elevated intact parathyroid hormone (1267.4 pg/ml) level. Sonography on the neck and 201Tl/99mTc parathyroid subtraction scan localized a left lower parathyroid tumor and fine needle aspiration confirmed the parathyroid origin. Diagnosis of 1 degree HPT could only be made from recurrent urolithiasis and X-ray picture of osteitis fibrosa cystica in the past. This patient presented the full-blown skeletal changes which are uncommonly seen nowadays. The characteristic sclerotic rims suggesting increased bone formation provides a further important clue for differential diagnosis of 1 degree HPT from other malignancies with osteolytic bone lesions.

Adult↗