Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

11 cases of primary hyperparathyroidism were seen during 1975-1988. Follow up has varied from 1-10 years. Renal disease in the form of renal calculi and nephro-calcinosis was observed in nine cases (81.8%). Two presented in chronic renal failure and required dialysis. Bone disease was found radiologically in six patients (54.5%); two had bone cysts in multiple bones while all six had subperiosteal bone erosion. Hypertension was found in three patients (27.3%). Proximal myopathy was observed in two cases (18.1%). One patient each presented with hypercalcaemic crisis, chondrocalcinosis and acute pancreatitis. The calcification of blood vessels and cornea was seen in two cases.
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PMID:Primary hyperparathyroidism. 238 Jan 35

The use of disodium etidronate (EHDP) for the treatment of calcinosis is complicated by the threat of drug-induced inhibition of skeletal mineralization. Adults with Paget's disease of bone treated for 6 months with 10-20 mg/kg/day of EHDP have been reported to show both a marked delay in mineralization and a diffuse excess of unmineralized bone matrix. Drug-induced bone disease is, however, a function of growth as well as of the dose and duration of therapy. Therefore, children treated with EHDP may respond differently to the drug-induced mineralization defect. A 10-year-old girl with dermatomyositis developed incapacitating ectopic calcification. After 9 months of therapy with 12 mg/kg/Day of EHDP, a small decrease in the calcinosis was accompanied by a dramatic increase in joint mobility. Bone mineral content of the radial diaphysis showed a failure to gain mineral density as expected with prepubertal growth (8 cm/year). Bone biopsy revealed a patchy excess of osteoid. Although the percentage of osteoid surface labeled by tetracycline was reduced, normal mineralization was evident in the double-labeled areas. In children, the mineralization defect occurring with EHDP treatment may be focal.
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PMID:Focal mineralization defect during disodium etidronate treatment of calcinosis. 680 82

Very few patients have undergone long-term peritoneal dialysis (PD). We report a case of a female patient on PD since 26 May 1979. Suffering from malignant hypertension, she developed renal failure in April 1979. The renal biopsy showed a severe vascular nephropathy. She was 50 years old, her body weight (BW) was 45 kg, and her height was 1.49 m. She refused hemodialysis. A Tenckhoff catheter was installed, and 12-hour intermittent PD (IPD), three times a week, was started in the dialysis center. Ten months later, she began nightly home IPD. In March 1985 she started continuous ambulatory PD (CAPD); she was nearly anuric. During the following years, she developed renal osteodystrophy and suffered from repeated hyperparathyroidism requiring multiple surgical interventions, osteomalacia, pseudotumoral calcinosis, and, finally, adynamic bone disease. She is now 67.5 years old, her BW is 34 kg, and she is still using CAPD. This patient has the same Tenckhoff catheter. She never developed peritonitis or an exit-site or tunnel infection. She used acetate dialysis solution for nearly six years and then lactate solution. Presently her peritoneal permeability is of the high-average type; dialysis adequacy (weekly Kt/V: 2.15, weekly peritoneal clearance: 58 L/1.73 m2) as well as nutritional parameters are satisfactory. She has moderate anemia without erythropoietin treatment. She maintains a good quality of life. Although the patient lost 11 kg in 17 years, she has maintained good nutritional status. Dialysis adequacy could be achieved despite anuria for more than 11 years. Small body size, absence of infection and catheter-related problems, healthy peritoneal membrane, good acceptance of the technique, and vigilance towards dietary habits may be the keys for satisfactory long-term PD.
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PMID:More than 17 years of peritoneal dialysis: a case report. 936 Jun 59

Biomineralization is the process by which hydroxyapatite is deposited in the extracellular matrix. Physiological mineralization occurs in hard tissues, whereas pathological calcification occurs in soft tissues. The first step of mineralization is the formation of hydroxyapatite crystals within matrix vesicles that bud from the surface membrane of hypertrophic chondrocytes, osteoblasts, and odontoblasts. This is followed by propagation of hydroxyapatite into the extracellular matrix and its deposition between collagen fibrils. Extracellular inorganic pyrophosphate, provided by NPP1 and ANKH, inhibits hydroxyapatite formation. Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes pyrophosphate and provides inorganic phosphate to promote mineralization. Inorganic pyrophosphate, pyridoxal phosphate, and phosphoethanolamine are thought to be the physiologic substrates of TNAP. These accumulate in the event of TNAP deficiency, e.g., in cases of hypophosphatasia. The gene encoding TNAP is mapped to chromosome 1, consists of 12 exons, and possesses regulatory motifs in the 5'-untranslated region. Inhibition of TNAP enzymatic activity suppresses TNAP mRNA expression and mineralization in vitro. Hypophosphatasia is an inherited systemic bone disease characterized by hypomineralization of hard tissues. The phenotype of hypophosphatasia is varied. To date, more than 200 mutations in the TNAP gene have been reported. Knockout mice mimic the phenotypes of severe hypophosphatasia. Among the mutations in the TNAP gene, c.1559delT is frequent in the Japanese population. This frameshift mutation results in the expression of an abnormally long protein that is degraded in cells. DNA-based prenatal diagnosis using chorionic villus sampling has been developed, but requires thorough genetic counseling. Although hypophosphatasia is untreatable at present, the recent success of enzyme replacement therapy offers promise. The problems presented by impaired mineralization in age-related chronic diseases, such as pathologic calcification and decreasing physiological mineralization are growing in importance. Strategies for preventing pathologic calcification using TNAP and NPP1 are in development. A nutrigenomic approach, based on the relationship between TNAP gene polymorphism and bone mineral density, is also discussed.
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PMID:The mechanism of mineralization and the role of alkaline phosphatase in health and disease. 2015 52

Impaired kidney function and subsequent skeletal responses play a critical role in disrupting phosphate balance in chronic kidney disease (CKD) patients with mineral and bone disorder (CKD-MBD). In patients with CKD-MBD, the inability of the kidney to maintain normal mineral ion balance affects bone remodeling to induce skeletal fracture and extraskeletal vascular calcification. In physiological conditions, bone-derived fibroblast growth factor 23 (FGF23) acts on the kidney to reduce serum phosphate and 1,25-dihydroxyvitamin D levels. In humans, increased bioactivity of FGF23 leads to increased urinary phosphate excretion, which induces hypophosphatemic diseases (e.g., rickets/osteomalacia). However, reduced FGF23 activity is associated with hyperphosphatemic diseases (e.g., tumoral calcinosis). In patients with CKD, high serum levels of FGF23 fail to reduce serum phosphate levels and lead to numerous complications, including vascular calcification, one of the important determinants of mortality of CKD-MBD patients. Of particular significance, molecular, biochemical and morphological changes in patients with CKD-MBD are mostly due to osteo-renal dysregulation of mineral ion metabolism. Furthermore, hyperphosphatemia can partly contribute to the development of secondary hyperparathyroidism in patients with CKD-MBD. Relatively new pharmacological agents including sevelamer hydrochloride, calcitriol analogs and cinacalcet hydrochloride are used either alone, or in combination, to minimize hyperphosphatemia and hyperparathyroidism associated complications to improve morbidity and mortality of CKD-MBD patients. This article will briefly summarize how osteo-renal miscommunication can induce phosphate toxicity, resulting in extensive tissue injuries.
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PMID:Osteo-renal regulation of systemic phosphate metabolism. 2143 15

Fibroblast growth factor 23 (FGF23) is produced by bone and reduces serum phosphate by inhibiting proximal tubular phosphate reabsorption and intestinal phosphate absorption. Excess actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia while deficient actions of FGF23 result in hyperphosphatemic tumoral calcinosis. In addition, FGF23 has been shown to prevent the development of hyperphosphatemia during the progression of chronic kidney disease-mineral and bone disorder. Epidemiological studies have indicated that high FGF23 levels are associated with unfavorable events including higher mortality, cardiovascular events, progression of CKD and fracture; however, these associations are not observed unequivocally and it is not evident why they are present. While FGF23 has been shown to be a hormone that regulates phosphate metabolism, it remains to be established whether FGF23 has roles other than regulating mineral homeostasis.
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PMID:Fibroblast growth factor 23 as a phosphotropic hormone and beyond. 2182 86

In chronic dialysis patients, ectopic, extraosseous calcifications can cause significant morbidity. Uremic tumoral calcinosis is an uncommon and severe complication of dialysis therapy. It is defined as deposition of dense nodular calcium-containing masses surrounding the large joints of the body, generally associated with the presence of high serum calcium-and-phosphorus product. We describe a 69-year-old woman submitted to long-term chronic hemodialysis that developed painful, bilateral hip tumors. Radiographic investigation showed extensive periarticular calcifications, and a bone biopsy was suggestive of adynamic bone disease and contained substantial amounts of aluminum. The lesions were surgically excised, and the histological analysis demonstrated amorphous, calcified material associated with densely collagenized connective tissue.
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PMID:Massive, painful tumoral calcinosis in a long-term hemodialysis patient. 2209 21

The authors describe a rare case of tumoral calcinosis (TC) of the thoracic spine in a 13-year-old boy with thoracic scoliosis. The patient presented with a 2-year history of back pain. He had no personal or family history of bone disease, deformity, or malignancy. Magnetic resonance imaging revealed a heterogeneously enhancing mass involving the T-7 vertebral body and the left pedicle. Computed tomography findings suggested that the mass was calcified and that this had resulted in scalloping of the vertebral body. The lesion was resected completely by using a left T-7 costotransversectomy and corpectomy. The deformity was corrected with placement of a vertebral body cage and pedicle screw fixation from T-5 to T-9. Pathological analysis of the mass demonstrated dystrophic calcification with marked hypercellularity and immunostaining consistent with TC. This represents the third reported case of vertebral TC in the pediatric population. Pediatric neurosurgeons should be familiar with lesions such as TC, which may be encountered in the elderly and in hemodialysis-dependent populations, and may not always require aggressive resection.
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PMID:Tumoral calcinosis presenting as a deformity of the thoracic spine. 2213 16

A 41-year-old male receiving hemodialysis for 10 years was referred to our hospital for multiple masses progressively growing in multiple joints and buttocks, which were diagnosed as giant tumoral calcinosis (TC) by radiographic findings. He had been hypercalcemic and hyperphosphatemic with high doses of vitamin D for chronic kidney disease-mineral and bone disorder. We then stopped vitamin D to manage the hypercalcemia and hyperphosphatemia; however, the TC did not regress after 1.5 years, thus the patient underwent renal transplantation. Subsequently, the TC gradually but almost completely disappeared over the next 1.5 years. A renal transplantation was thus found to be useful for the successful treatment of TC.
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PMID:Complete resolution of tumoral calcinosis after renal transplantation. 2251 62

Chronic kidney disease-mineral and bone disorder (CKD-MBD) affects life expectancy through vascular calcification, and impairs patient's activity of daily living (ADL) and quality of life (QOL) through bone fracture and periarticular calcification. In CKD patients, vitamin D deficiency and secondary hyperparathyroidism impairs bone strength, and muscle dysfunction related to vitamin D deficiency also causes easy fall, leading to the high risk of bone fracture. Bone fracture not only aggravates ADL and QOL but increases the risk of mortality. Periarticular calcification such as tumoral calcinosis in relation to CKD-MBD causes restricted range of articular motion, leading to the deterioration of patient's ADL and QOL. Because bone fragility and tumoral calcinosis occurs in relation to CKD-MBD, the appropriate management of CKD-MBD is madatory.
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PMID:[Kidney and bone update : the 5-year history and future of CKD-MBD. Disorders of musculoskeletal system in CKD ; bone fracture and periarticular calcification]. 2275 Sep 32


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