Hyperparathyroid bone disease

NSHPT in most cases presents within the first six months of life. Affected infants have severe, symptomatic, PTH-dependent hypercalcemia, along with the bony changes of severe hyperparathyroidism. Infants with NSHPT can exhibit polyuria, dehydration, hypotonia, and failure to thrive (Brown et al, 1997 Eftekhari and Yousefzadeh, 1982 Grantmyre, 1973 Heath, 1989a Marx etal, 1985). A prominent feature of the disease is the associated hyperparathyroid bone disease, which can be associated with multiple fractures. Rib fractures can in some cases produce a... 

Intermediate concentrations are seen in low-turnover adynamic (aplastic) disease and early osteitis fibrosa. Considerable overlap in intact PTH concentrations is apparent among the various forms of renal osteodystrophy. In dialysis patients, cut-points ( decision levels ) of less than 100 or 150 pg/mL and greater than 250 to 300 pg/mL have been suggested for distinguishing patients with low-turnover and high-turnover bone disease, respectively. A reasonable therapeutic goal for intact PTH (first generation) concentrations is two to four times the upper limit of the reference interval to prevent parathyroid-suppressed, adynamic, and hyperparathyroid bone diseases. ... 

Osteitis fibrosa (hyperparathyroid bone disease) is the most common high-turnover bone disease. This disorder is caused by the high concentrations of serum PTH in secondary hyperparathyroidism. Secondary hyperparathyroidism is a consequence of the hypocalcemia associated with hyperphosphatemia and l,25(OH)2D deficiency. Hyperphosphatemia is a result of the kidneys inability to excrete phosphate. l,25(OH)2D deficiency results from the inability of the kidneys to synthesize l,25(OH)2 because of decreased renal mass and suppression of 25(OH)D-la-hydroxylase activity by high concentrations of phosphate. Deficiency of l,25(OH)2D leads to reduced intestinal absorption of calcium and reduced inhibition of PTH secretion by l,25(OH)2D. Skeletal resistance to PTH also contributes to the hypocalcemia and secondary hyperparathyroidism. 

Potter, D. E., Wilson, S. J., and Ozonoff, M. B., Hyperparathyroid bone disease in children undergoing long-term hemodialysis treatment with vitamin D. /. Pediatr. 85, 60-66 (1974). 

Other forms of uremic bone disease also occur. They include osteosclerosis (rugger jersey spine), nutritional osteomalacia, aluminum-induced osteodystrophy (low-turnover bone disease, or osteomalacia), and mixed uremic osteodystrophy (hyperparathyroid bone disease and defective mineralization) (M17). 

Hyperphosphatemia is common in patients with end-stage renal disease (ESRD), since a large fraction (60-70%) of dietary phosphorus is absorbed and normally excreted by the kidneys, and as kidney function deteriorates, less phosphorus is exereted by the kidneys (Emmett 2004). Dietary restrictions have insuffieient effect. The condition may have serious consequences. Hyperphosphatemia stimulates parathyroid hormone and suppresses vitamin D3 production, and thus induces hyperparathyroid bone disease. In addition, it leads to myocardial and vascular calcification and cardiac microcirculatory abnormalities, which results in cardiac causes of death. Phosphate levels henee should be eontrolled early in the... 

A. E. Sizemore, G. W. Arnaud, C. D. "Etiology of Hyperparathyroidism and Bone Disease During Chronic Hemodialysis. III. Evaluation of Parathyroid Suppressability". J. Clin. Invest. (1973), 52, 173-180. 

Secondary hyperparathyroidism Increased secretion of parathyroid hormone from the parathyroid glands caused by hyperphosphatemia, hypocalcemia, and vitamin D deficiency that result from decreased kidney function. It can lead to bone disease (renal osteodystrophy). 

Renal osteodystrophy is a complex disorder with several pathogenic factors. Histological evidence of bone disease is common in early renal failure and deficits in calcitriol synthesis seems to be an important factor in the pathogenesis of secondary hyperparathyroidism in early CRF. The most common component is osteitis fibrosa manifested as subperiosteal resorption of bone. This is due to decreased excretion as well as increased secretion of parathyroid hormone. In CRF small increments of serum phosphorus cause small decreases in serum calcium. 

Patients with chronic renal failure develop hyperphosphatemia, hypocalcemia, secondary hyperparathyroidism, and severe metabolic bone disease. The secondary hyperparathyroidism is thought to be due to hyperphosphatemia and decreased 1, 25-(OH)2 formation. Oral or intravenous l,25-(OH)2D3 (calcitriol) therapy along with oral phosphate-binding agents and calcium supplementation is effective in reducing the effects of renal osteodystrophy. 

Contraindications Primary or secondary hyperparathyroidism, including hypercalci-uria (renal calcium leak), hypomagnesemic states (serum magnesium less than 1.5 mg/dl), bone disease (osteoporosis, osteomalacia, osteitis), hypocalcemic states (e.g., hypoparathyroidism, intestinal malabsorption), normal or low intestinal absorption and renal excretion of calcium, enteric hyperoxaluria, and patients with high fasting urinary calcium or hypophosphatemia. 

It is indicated in osteoporosis, hypoparathyroidism, hyperparathyroidism (with bone disease), renal osteodystrophy, nutritional and malabsorptive rickets, hypophosphataemic vitamin D resistant rickets and osteomalacia. 

The choice of vitamin D preparation to be used in the setting of chronic kidney disease depends on the type and extent of bone disease and hyperparathyroidism. Individuals with vitamin D deficiency or insufficiency should first have their 25(OH)D levels restored to normal (above 30 ng/mL) with vitamin D. l,25(OH)2D3 (calcitriol) rapidly corrects... 

Vitamin D-binding protein and its associated vitamin are lost in nephrotic urine. Biochemical abnormalities in nephrotic patients (children and adults) include hypocalcemia, both total (protein-bound) and ionized hypocalciuria, reduced intestinal calcium absorption and negative calcium balance reduced plasma 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, surprisingly, also 1,25-dihydroxycholecalciferol and blunted response to parathormon (PTH) administration and increased PTH levels. Clinically, both osteomalacia and hyperparathyroidism have been described in nephrotic patients, more commonly in children than in adults, but bone biopsies are commonly normal, and clinically significant bone disease is very rare in nephrotic subjects. There is, however, evidence that patients with renal failure accompanied by nephrotic range proteinuria may be particularly prone to develop renal osteodystrophy. 

These in vitro findings allow us to suggest that transferrin receptor-mediated uptake of Al might, besides other factors such as vitamin D, high calcium dialysate or CaC03 intake, play a role in the development of hypoparathyroidism associated with Al bone disease. The exact mechanism by which Al-transferrin suppresses iPTH secretion remains to be elucidated [253]. Hyperparathyroidism may afford the bone some protection against the toxic effects of Al [17]. 

Hyperparathyroidism and aluminium hydroxide lead to aluminium-related bone disease however, total parathyroidectomy does not lead to failure of aluminium mobilization after renal transplantation. This man had satisfactory graft function, and the aluminium excretion that was achieved by deferoxamine suggests that the renal transplant was not the limiting factor for the mobihzation of aluminium. The most likely explanation was that he developed adynamic bone through a combination of vitamin D deficiency, hypoparathyroidism, and aluminium deposition. Vitamin D supplementation failed to prevent the osteodystrophy on its own. When aluminium chelation therapy was used, bone healing occurred and his symptoms improved. 

Slight or moderate elevations in serum TR-ACP activity often occur in Paget s disease, in hyperparathyroidism with skeletal involvement, and in the presence of malignant invasion of the bones by cancers, such as breast cancer in women. Increased concentrations of the osteoclast-derived AGP are also present in serum in osteoclastoma (giant-cell tumor), an osteoclastic neoplasm, and in osteopetrosis (marble bone disease) in which the osteoclasts fail to resorb bone. High concentrations... 

Acute hemorrhagic and edematous pancreatitis Healing phase of bone disease of treated hyperparathyroidism, hyperthyroidism, and hematological malignancies (hungry bone syndrome)... 

Elevated concentrations of telopeptides and DPD have been reported in osteoporosis, Paget s disease, metastatic bone disease, primary and secondary hyperparathyroidism, hyperthyroidism, and other diseases with increased bone... 

BAP is increased in metabolic bone diseases, including osteoporosis, osteomalacia and rickets, hyperparathyroidism, renal osteodystrophy, and thyrotoxicosis, and in individuals with acromegaly, bony metastases, glucocorticoid excess, Paget s disease, and other disorders with increased bone formation." ... 

Marked elevations of plasma peptide hydroxyproline have been observed by Dubovsky et al. in chronic renal failure (D7). The highest levels were seen when uremia and severe bone disease occurred together. Removal of the parathyroids in four patients (three primary and one secondary hyperparathyroidism) was associated with return to normal levels when renal function was normal, and significant reduction when renal failure was present. It seems possible that plasma peptide hydroxyproline might be a rapidly changing and sensitive indicator of bone metabolism which could be studied even with renal impairment, a major obstacle to most current techniques in the diagnosis of hyperparathyroid states. 

The earliest literature on alkaline phosphatase (F21, R11-R14) has emphasized the osteoblastic source of serum alkaline phosphatase in growing children and in patients with bone disease, such as hyperparathyroidism (D12), Paget s disease, etc. A voluminous literature has followed (J2, K2, K17, M12, M31, Nl, S45, T3, VI, V2). 

Renal osteodystrophy (ROD)—The condition resulting from sustained metabolic changes that occur with chronic kidney disease including secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, and vitamin D deficiency. The skeletal complications associated with ROD include osteitis fibrosa cystica (high bone turnover disease), osteomalacia (low bone turnover disease), adynamic bone disease, and mixed bone disorders. 

Despite the postulated connection between parathyroid hormone activity and citric acid metabolism, plasma citrate concentration is normal in cases of hyperparathyroidism unless there is active bone disease present, in which case it may be raised (Wl). Plasma alkaline phosphatase is also raised only in the presence of active osteitis fibrosa. 

Patients with chronic renal failure often have hypocalcaemia due to the inability of renal cells to make 1,25 dihydroxycholecalciferol. Secondary hyperparathyroidism and bone disease may result. 

Hyperphosphatemia occurs commonly in chronic renal failure. The increased phosphate level direcdy stimulates PTH secretion and also has secondary effects due to the reduction in serum Cd . Because renal function is impaired, the increased PTH is unable to increase phosphate excretion sufficiently to avoid ongoing phosphate retention. The chronic secondary hyperparathyroidism may result in a bone disease called renal osteodystrophy. 

Bone disease is a frequent consequence of chronic renal failure and dialysis. Pathologically, the lesions are typical of hyperparathyroidism, adynamic bone disease, deficiency of vitamin D (osteomalacia), or a combination of the above. The underlying defect reflects increased phosphate and decreased calcium, leading to secondary events that strive to preserve circulating levels of Ca at the expense of bone. 

The principal adverse effect of cinacalcet is hypocalcemia. The drug should not be used if the initial serum calcium is <8.4 mg/dL serum calcium and phosphate concentrations should be measured within one week and PTH should be measured within 4 weeks of therapy initiation. Adynamic bone disease may develop in patients with secondary hyperparathyroidism, so the drug should be discontinued or the dose decreased if the PTH level falls below 150 pg/mL. 

On the wider scale, ionised calcium in sera measured with the calcium ion-selective electrode have helped in studying the direct effect of calcium on the hyperparathyroidism of chronic renal failure when it was shown that rats on low calcium diet developed larger parathyroids and more severe bone disease at the end of four weeks while diets with above normal calcium levels produced no additional benefits [130]. Other studies include the relation between hypercalcemia and normal ionised serum calcium in a case of myelomatosis [86], the detection of hypocalcemia in susceptible neonates [68], and studies on serum ionised calcium changes following citrated blood transfusion in anaesthetised subjects [93]. The transfusion studies showed six patients during anaesthesia to have a decrease of 0.135 mmol dm" after 500 cm and 0.15 mmol dm" after 1000 cm blood, respectively. However, the calcium ion concentration increased by a mean of 0.075 mmol dm" in 10 min following complete infusion of the blood [93]. 

Chronic renal failure. Normal kidney function is needed for the la-hydroxylation reaction that produces 1,25-DHCC. In chronic renal failure a cascade of events is triggered, leading to secondary hyperparathyroidism, which can progress to tertiary hyperparathyroidism and renal bone disease. 

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