Osteitis fibrosa

Osteitis fibrosa cystica Renal osteodystrophy Osteosclerosis Anticonvulsant treatment... 

ROD progresses insidiously for several years before the onset of symptoms such as bone pain and fractures. Skeletal complications include osteitis fibrosa cystica (high bone turnover), osteomalacia (low bone turnover) and adynamic bone disease. When ROD symptoms appear, the disease is not easily amenable to treatment. 

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. 

Osteitis fibrosa does not occur, as in renal osteodystrophy. The common features that appear to be important in this group of diseases are malabsorption of calcium and malabsorption of vitamin D. Liver disease may, in addition, reduce the production of 25(OH)D from vitamin D, although its importance in all but patients with terminal liver failure remains in dispute. The malabsorption of vitamin D is probably not limited to exogenous vitamin D. The liver secretes into bile a substantial number of vitamin D metabolites and conjugates that are reabsorbed in (presumably) the distal jejunum and ileum. Interference with this process could deplete the body of endogenous vitamin D metabolites as well as limit absorption of dietary vitamin D. 

The major problems of chronic renal failure that impact on bone mineral homeostasis are the loss of l,25(OH)2D and 24,25(OH)2D production, the retention of phosphate that reduces ionized calcium levels, and the secondary hyperparathyroidism that results. With the loss of l,25(OH)2D production, less calcium is absorbed from the intestine and less bone is resorbed under the influence of PTH. As a result hypocalcemia usually develops, furthering the development of hyperparathyroidism. The bones show a mixture of osteomalacia and osteitis fibrosa. 

The choice of vitamin D preparation to be used in the setting of chronic renal failure in the dialysis patient depends on the type and extent of bone disease and hyperparathyroidism. No consensus has been reached regarding the advisability of using any vitamin D metabolite in the predialysis patient. l,25(OH)2D3 (calcitriol) will rapidly correct hypocalcemia and at least partially reverse the secondary hyperparathyroidism and osteitis fibrosa. Many patients with muscle weakness and bone pain gain an improved sense of well-being. 

Carmichael KA, Fallon MD, Dalinka M, et al. 1984. Osteomalacia and osteitis fibrosa in a man ingesting aluminum hydroxide antacid. Am J Med 76 1137-1143. 

Anticonvulsant treatment Fibrogenes imperfecta ossium Osteitis fibrosa cystica Osteomalacia Osteoporosis Osteopenia Osteosclerosis Renal osteodystrophy Rickets... 

OH)2D3 concentrations. Low l,25-(OH)2D3 results in little to no intestinal calcium absorption for soft tissue needs. Thus, blood calcium can be low and secondary hyperparathyroidism develops. The inability to regulate renal handling of phosphate by PTH leads to phosphate-mediated repression of ionized calcium. Serious osteodystrophic lesions occur because of high PTH activity on bone resorption resulting in osteitis fibrosa and osteosclerosis. 

One female and one male patient had hyperparathyroidism with elevated serum alkaline phosphatase activities and extensive bone changes characteristic of generalized osteitis fibrosa cystica. In both instances, the serum acid phosphatase activity of the serum fell to normal values after removal of the parathyroid adenoma despite transitorily increased serum alkaline phosphatase activity. The fifth patient was a female with osteopetrosis involving the major part of the skeleton. The serum acid phosphatase was 8.7 K.A. units, the highest in the control series— yet the serum alkaline phosphatase was within normal limits. It would appear, therefore, that some patients with skeletal disease may have a slight but definitely elevated serum acid phosphatase activity, at least as determined by the Gutman method (GIO, G14), which cannot be explained by concurrent prostatic carcinoma or by a spillover of alkaline phosphatase activity to a pH of 5.0. 

The main hmiting factor in obtaining an optimal response to epoetin is the adequacy of the patient s iron stores (32,33) the response is abated in the presence of iron deficiency, occult blood loss, hemolysis, and other hematological diseases (34,35). Other causes of an inadequate response to epoetin include concurrent infection or inflammatory disease (1), aluminium toxicity, vitamin deficiencies, secondary hyperparathyroidism (36,37), and osteitis fibrosa (38,39). 

Coevoet B, Sebert JL, DeGueris J, et al. Adverse effect of vitamin D metabohtes on osteitis fibrosa in patients on chronic hemodialysis critical role of induced hyperphosphatemia. Miner Electrolyte Metab 1979 2 217. 

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. ... 

Figure 49-16 Intact PTH in assessing parathyroid function in end-stage renal disease. Dialysis patients were separated into those with early and advanced osteitis fibrosa, osteomalacia, and aplastic disease by quantitative histomorphometric analysis of undecalcified bone biopsies. (From Segre GV, Sherrard DJ, Pandian /WR, et al. Intact PTH (IRMA) II New applications to issues in parathyroid hormone and mineral metabolism. San Juan Capistrano, Calif Nichols Institute, 1989.)...

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. 

Voigts A, Felsenfeld AJ, Andress D, Llach E Parathyroid hormone and bone histology response to hypocalcemia in osteitis fibrosa. Kidney Int 1984 25 445-52. 

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. 

A5. Albright, F., Butler, A. M., Hampton, A. D., and Smith, P., Syndrome characterised by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in femaies. New Engl. J. Med. 216, 727-746 (1937). 

Most patients who require dialysis have a normocytic normochronic anemia and a hypoproliferative bone marrow. As erythropoiesis decreases with advancing renal disease, iron shifts from circulating red cells to the reticuloendothelial system, leading to high serum ferritin levels. Repeated blood transfusion is also a common cause of iron overload and hyperferritinemia. Clearly the most important cause of the anemia of chronic renal failure is decreased erythropoietin production by the kidneys uremic patients have much lower plasma erythropoietin levels than comparably anemic patients with normal renal function (E8). Less important causes are shortened red cell survival, iron or folate deficiency, aluminum intoxication, and osteitis fibrosa cystica (E8). Uremic retention products such as methylguanidine (G10) and spermidine (R2) may also have an adverse effect on erythropoiesis. 

The clinical end product of the pathophysiological processes just described is usually osteitis fibrosa cystica. Skeletal raidography may show characteristic... 

Osteoporosis and osteitis fibrosa cystica Metastatic calcifications vi. Neurologic changes Secondary hyperparathyroidism a. Etiology... 

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. 

When the concentration of phosphate in plasma rises to the level where precipitation of calcium phosphate occurs, ionic calcium is depressed and parathyroid stimulation follows. This stimulation is continuous and progressive because the parathyroids are unable to restore the calcium concentration to normal, and enormous enlargement of the parathyroids follows (N8). Continuing parathyroid overactivity makes the bones more soluble than calcium phosphate at pH 7.4 with the result that there is a continuous transfer of mineral from the skeleton (which develops osteitis fibrosa) to blood vessel walls and soft tissues in gaieral (which become calcified). Parathyroidectomy is the only logical treatment and this has been done by Stanbuiy et al. (S5). 

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