Metabolic bone diseases

Due to its anti-resorptive effects, calcitonin has been widely used to treat a variety of metabolic bone diseases, including osteoporosis. However, the availability of more potent drugs has lead to a decline in the clinical use of calcitonin. 

Declining renal function disrupts the homeostasis of the systems regulated by the kidney, leading to fluid and electrolyte imbalances, anemia, and metabolic bone disease. 

Studies have demonstrated that reversal of metabolic acidosis can improve bone disease associated with CKD.38 Serum bicarbonate levels should be maintained at 22 mEq/L (22 mmol/L) in patients with bone disease associated with CKD.39 The treatment of metabolic acidosis is described below. 

Describe the etiology and risk factors for liver complications and metabolic bone disease in patients receiving PN. 

Factors that can predispose patients to developing metabolic bone disease include deficiencies of phosphorus, calcium, and vitamin D vitamin D and/or aluminum toxicity amino acids and hypertonic dextrose infusions chronic metabolic acidosis corticosteroid therapy and lack of mobility.35,39 Calcium deficiency (due to decreased intake or increased urinary excretion) is one of the major causes of metabolic bone disease in patients receiving PN. Provide adequate calcium and phosphate with PN to improve bone mineralization and help to prevent metabolic bone disease. Administration of amino acids and chronic metabolic acidosis also appear to play an important role. Provide adequate amounts of acetate in PN admixtures to maintain acid-base balance. 

Vitamin D toxicity has been suggested as a cause of metabolic bone disease. However, vitamin D deficiency results in bone loss, and data on vitamin D excess and metabolic bone disease remain controversial. 

Encourage patients on long-term PN to engage in regular low-intensity exercise. Yearly bone density measurements also should be performed on patients on long-term PN and when metabolic bone disease is suspected. 

Reduction in the serum 1,25-dihydroxyvitamin D concentration has been reported as an indicator of increased lead absorption or lead levels in the blood (Rosen et al. 1980). Lead inhibits the formation of this active metabolite of vitamin D, which occurs in bone mineral metabolism (EPA 1986a Landrigan 1989). Children with PbB concentrations of 12-120 pg/dL lead showed decreased serum 1,25-dihydroxyvitamin D concentrations comparable to those found in patients with hypoparathyroidism, uremia, and metabolic bone disease (Mahaffey et al. 1982 Rosen et al. 1980). This biomarker is clearly not specific for lead exposure and several diseases can influence this measurement. 

Sr, as the strontium ion (Sr2+), is used for pain palliation in patients with metastatic bone disease. The strontium ion is a calcium ion mimic, being taken up in metabolically active bone such as cancer. 89Sr is a therapeutic radionuclide with a half-life of 50.53 days, emitting a 1.49 MeV [3 particle on decay. Several recent reviews discuss the use of radionuclides and their complexes as pain palliation agents in metastatic bone disease.18,212-215... 

Glimcher, M.J. (1998) Metabolic Bone Disease and Related Disorders (eds Avioli and Krane), Academic Press, London, pp. 23—50. 

See Chap. 93, Osteoporosis and Other Metabolic Bone Diseases, authored by Mary Beth O Connell and Sheryl F. Vondracek, for a more detailed discussion of this topic. 

Visual blurring Metabolic bone disease Sedation... 

Phenytoin, carbamazepine, phenobarbital, oxcarbazepine, and valproic acid may interfere with vitamin D metabolism, causing asymptomatic high-turnover bone disease with normal bone density or decreased bone mineral... 

Consequences of metabolic acidosis include renal bone disease, reduced cardiac contractility, predisposition to arrhythmias, and protein catabolism. 

Frost HM (1973) Bone remodeling and its relationships to metabolic bone disease. Charles C. Thomas, Springfield, MA... 

Hofbauer LC, Heufelder AE (2000) Clinical review 114 hot topic. The role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in the pathogenesis and treatment of metabolic bone diseases. J Clin Endocrinol Metab 85 2355-2363... 

NO is recognized as a mediator of bone cell metabolism, where it regulates osteoblast and osteoclast activity [141-143]. Osteoporosis, which frequently occurs in postmenopausal women, is a systemic skeletal disease associated with abnormal bone resorption. Addition of NO or NO donors to osteoclasts in vitro results in a reduction in bone resorption, whereas NO synthase inhibitors increase bone resorption, both in vitro and in vivo. Further research has shown that NO reduces bone resorption, via inhibition of the cysteine protease cathepsin K, which is believed to be a key protease in bone resorption. Most of the NO donors, i.e., nitroglycerin, 3-... 

Bisphosphonates are drugs of great interest in a number of metabolic bone diseases [119]. This therapeutic class comprises bis(phosphonic acids) and, more recently, bis(phosphonic acid) esters. The former are hydrophilic and poorly bioavailable, and they are generally not metabolized. In contrast, bis(phosphonic acid) esters may be more prone to biotransformation, as exemplified with the lead compound known as U-91502 (9.51 in Fig. 9.11). 

W. K. Sietsema, F. H. Ebetino, Bisphosphonates in Development for Metabolic Bone Disease , Exp. Opin. Invest. Drugs 1994, 3, 1255-1276. 

Centre for Metabolic Bone Disease, Hull, United Kingdom p.albertazzi hull.ac.uk... 

Calcium and phosphorus metabolism Calcium and phosphorus metabolism is influenced by estrogens use caution in patients with metabolic bone diseases associated with hypercalcemia or in renal insufficiency. 

Children The use of isotretinoin in pediatric patients less than 12 years of age has not been studied. Carefully consider isotretinoin use in pediatric patients 12 to 17 years of age, especially for those patients in whom a known metabolic or structural bone disease exists. 

Dawson-Hughes, B. (2006a). Calcium and vitamin D. In "Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism" (M. J. Favus, ed.), pp. 257-259. The American Society for Bone and Mineral Research, Washington DC. 

Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone tissue. This will lead to bone fragility and consequent increase in bone fracture risk. Mean bone mineral density (BMD) is measured with dual X-ray absorptiometry (DEXA) and expressed in Tsc (Tscore). WHO standards are a Tsc that is 1 standard deviation (SD) below mean BMD is graded as normal bone, Tsc between 1 and 1.5 SD below mean BMD is graded as osteopenia and a Tsc of more than 2.5 SD below mean BMD is graded as osteoporosis. When the Tsc is below 1.5 SD mean BMD prevention of osteoporosis must be initiated. Primary osteoporosis is caused mainly by hormone deflciency in both women and men. Secondary osteoporosis may result from endocrine, metabolic, nutritional and autoimmune causes or from immobility because of trauma. Also the use of medicaments such as corticosteroids may be contributing. 

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. 

Vitamin D3 is transported to liver where it undergoes a hydroxylation at C-25 into 1a,25-dihydroxyvitamin D3 (calcitriol) (Fig. 64). In the kidney, it undergoes further hydroxylations at different sites, depending on the serum Ca + concentration. The most biologically active metabolite of vitamin D3 is calcitriol, which plays important roles in the regulation of calcium and phosphorus metabolism. It is used for treating bone diseases, but is also involved in the cell proliferation and the inducement of cell differentiation [151]. 

Plicamycin is a cytotoxic antibiotic (see Chapter 54) that has been used clinically for two disorders of bone mineral metabolism Paget s disease and hypercalcemia. The cytotoxic properties of the drug appear to involve its binding to DNA and interruption of DNA directed RNA synthesis. The reasons for its usefulness in the treatment of Paget s disease and hypercalcemia are unclear but may relate to the need for protein synthesis to sustain bone resorption. The doses required to treat Paget s disease and hypercalcemia are about one tenth the amounts required to achieve cytotoxic effects. 

In mild forms of malabsorption, vitamin D (25,000-50,000 units three times per week) should suffice to raise serum levels of 25(OH)D into the normal range. Many patients with severe disease do not respond to vitamin D. Clinical experience with the other metabolites is limited, but both calcitriol and calcifediol have been used successfully in doses similar to those recommended for treatment of renal osteodystrophy. Theoretically, calcifediol should be the drug of choice under these conditions, because no impairment of the renal metabolism of 25(OH)D to l,25(OH)2D and 24,25(OH)2D exists in these patients. Both calcitriol and 24,25(OH)2D may be of importance in reversing the bone disease. However, calcifediol is no longer available. 

Patients with nephrotic syndrome can lose vitamin D metabolites in the urine, presumably by loss of the vitamin D-binding protein. Such patients may have very low 25(OH)D levels. Some of them develop bone disease. It is not yet clear what value vitamin D therapy has in such patients, because therapeutic trials with vitamin D (or any other vitamin D metabolite) have not yet been carried out. Because the problem is not related to vitamin D metabolism, one would not anticipate any advantage in using the more expensive vitamin D metabolites in place of vitamin D itself. 

Alendronate sodium is indicated for prevention of glucocortoid-induced bone loss. Rapid bone loss occurs after transplantation, placing these patients at increased risk for fractures. Because of improving longterm survival, attention to metabolic bone disease should occur early in the posttransplant course so that the risk of complications might be lessened. 

Heiner JP, Joyce MJ, Carter JR, Makley JT. Atraumatic posterior pelvic ring fractures simulating metastatic disease in patients with metabolic bone disease. Orthopedics 1994 17(3) 285-9. 

Brown, EM, Bai, M and Poliak, MR. Familial benign hypocalciuric hypercalcemia and other syndromes of altered responsiveness to extracellular calcium. In Metabolic Bone Diseases and Clinically Related Disorders, (third edition ed.), edited by Krane S and Avioli LV. San Diego, CA Academic Press, 1997, p. 479 199... 

Chronic disturbances in calcium homeostasis can also produce problems in bone calcification. Likewise, various metabolic bone diseases can alter blood calcium levels, leading to hypocalcemia or hypercalcemia. Some of the more common metabolic diseases... 

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