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)

Bone involvement is a central feature of multiple myeloma (MM). We investigated whether serum markers of osteoblastic and osteoclastic activity correlate with the presence of bone disease and survival in 313 MM patients enrolled in a phase III trial (E9486). Five markers were measured, including osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), bone alkaline phosphatase (BAP), carboxy-terminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). We analysed the relationship between serum levels of these markers and the presence of bone manifestations, and survival. Serum levels of ICTP and BAP correlated significantly with bone pain, lesions and fractures. Serum level of ICTP was also higher in stage II-III compared with stage I disease. The serum level of ICTP was significantly associated with shortened survival in the univariate analysis. The median survival times were 4.1 and 3.5 years for low and high ICTP respectively (P = 0.02). There was a strong relationship between ICTP and beta-2-micrgolobulin (B2M). ICTP stands out as a significant marker of bone disease. Incorporation of these markers into clinical trials assessing the use of bisphosphonates in MM is needed to determine whether they might serve as indicators of effectiveness of these agents.
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PMID:Prognostic value of serum markers of bone metabolism in untreated multiple myeloma patients. 1084 78

Pseudohypoparathyroidism (PHP) is a disorder characterized by hypocalcemia and secondary hyperparathyroidism caused by primarily renal resistance to the effects of parathyroid hormone (PTH). However, as an indication of normal PTH responsiveness in bone, some patients with PHP develop skeletal disease because of longstanding secondary hyperparathyroidism. A patient is described with hypocalcemia, hyperphosphatemia, marked secondary hyperparathyroidism, and an increased alkaline phosphatase level. Subsequent evaluation revealed a diagnosis of PHP type Ib. The patient had radiographic evidence of skeletal disease caused by secondary hyperparathyroidism. A urinary level of N-telopeptide cross-links of type I collagen (NTX) was elevated markedly. Bone mineral density (BMD) was in the normal range at all measured sites, with BMD at the spine being higher than at the femur and distal radius. Treatment was initiated with calcium and calcitriol. Seven months later, calcium and PTH levels had normalized. The level of urinary NTX fell by 83%. Spinal BMD improved by 15%, and BMD at the femoral neck improved by 11%. Radial BMD was unchanged. This case emphasizes the importance of evaluating patients with PHP for hyperparathyroid bone disease and shows that correction of secondary hyperparathyroidism in patients with PHP can result in a significant suppression of previously accelerated bone turnover and to substantial gains in BMD at sites containing a major percentage of cancellous bone. The case also implies that assessment of bone turnover with urinary NTX and measurement of BMD with dual-energy X-ray absorptiometry (DEXA) may be useful in following the response of the skeleton to therapy in these patients and suggests the need for more studies of both NTX and BMD in patients with PHP.
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PMID:Serial changes in bone mineral density and bone turnover after correction of secondary hyperparathyroidism in a patient with pseudohypoparathyroidism type Ib. 1089 92

Organ transplantation is associated with relevant bone loss. Bone loss of up to 20% of pretransplant bone mineral density (BMD) values within the first year after kidney, liver, heart and lung transplantation has been reported. Patients undergoing transplantation of hematopoietic stem cells provide an interesting model to study transplantation-induced bone loss, especially because most patients do not have preexisting bone disease. A longitudinal study was performed in 81 patients undergoing bone marrow or peripheral blood stem cell transplantation. BMD was determined by dual-energy X-ray absorptiometry before transplantation, at discharge from the hospital, and at 6 and 12 months after transplantation in all 81 patients. In 35 patients BMD was re-evaluated 24 months after transplantation. Vitamin D and parathyroid hormone, bone alkaline phosphatase as a marker of bone formation, and N-terminal telopeptide of type I collagen as a marker of bone resorption were assessed before transplantation and in the short-term follow-up 14 and 28 days after transplantation. The majority of patients (72%) showed normal BMD before transplantation. However, lower BMD was observed in patients who had received high-dose cytoreductive chemotherapy before transplantation compared with those who had received no chemotherapy or only hydroxyurea. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (1000 IU/day), the mean rate of bone loss during the first year was 7.2 +/- 6.3% at the lumbar spine, 11.9 +/- 8.1% at the femoral neck and 3.8 +/- 2.5% at the total body compartment. Evaluation of the pattern of bone loss during the first year demonstrated that the amount of bone loss was largest within the first 40 days after transplantation and small during the second half of the first year after transplantation. The majority of patients showed vitamin D deficiency and secondary hyperparathyroidism. Bone formation was normal before and after transplantation, whereas bone resorption was dramatically increased before and after transplantation. Exposure to glucocorticoids was associated with higher bone loss at spine and femoral neck but not at the total body compartment. Our data demonstrate rapid bone loss in patients undergoing transplantation of hematopoietic stem cells. Bone turnover is characterized by biochemical uncoupling of bone resorption and bone formation, changes interestingly pre-existing before transplantation. The observed alterations in bone mass and metabolism emphasize the importance of clinical trials with antiresorptive agents to prevent and treat post-transplantation osteoporosis in this group of patients.
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PMID:Bone loss in long-term survivors after transplantation of hematopoietic stem cells: a prospective study. 1092 25

Biochemical markers of bone resorption have been used to characterize metabolic bone disease and assess therapeutic response. Most studies have used the urinary measurement of collagen crosslinks, but serum assays have recently been developed that may have less analytic and biologic variability. In the present study, we measured urine and serum N- and C-terminal crosslinked telopeptides of type I collagen (NTX and CTX) and serum bone sialoprotein (BSP) in postmenopausal women with or without hormone replacement therapy (HRT) and in men of similar age. In these populations, the variability of serum and urine markers was similar, except that serum NTX showed somewhat lower variability in postmenopausal women. Urine and serum assays correlated well with one another and were significantly lower in postmenopausal women on HRT compared with untreated women. The difference in women on HRT was similar for sNTX, uNTX and BSP (35-40%) and greater for sCTX and uCTX (52-53%). There was an inverse correlation between markers and bone mineral density, largely attributable to the high correlation in women not on HRT. Fractional excretion of NTX and CTX were estimated at 0.20+/-0.07 and 0.44+/-0.11, respectively. These values were independent of the concentration of the marker or of creatinine in the urine. We conclude that serum markers are useful measures of bone resorption in these populations, in whom the use of such markers is likely to be helpful in the management of osteoporosis.
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PMID:Comparison of serum and urine assays for biochemical markers of bone resorption in postmenopausal women with and without hormone replacement therapy and in men. 1098 62

Low bone density, fractures, and kyphosis complicate the lives of adults with cystic fibrosis (CF), and inflammatory cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha) that may alter bone metabolism have been previously found to be increased in the lungs and serum of CF patients. The objective of this prospective study was to determine the impact of lung infection on bone physiology in 17 adult CF patients. Serum osteocalcin, a marker of bone formation; urine N-telopeptides of type I collagen and free deoxypyridinoline, both of which are markers of bone breakdown; serum cytokines (TNF-alpha, IL-1beta, and IL-6); and general inflammatory markers (serum C-reactive protein [CRP] and chondrex) were measured at the beginning and end of treatment for an acute exacerbation of lung infection and again 3 wk later. After treatment with conventional antibiotics, decreases in N-telopeptides (147.3 +/- 77.5 [mean +/- SEM] versus 95.5 +/- 57.3 bone collagen equivalents (BCE)/mmol creatinine, p = 0.0014), deoxypyridinoline (8.42 +/- 2.8 versus 6.8 +/- 3.0 mmol/mmol creatinine, p = 0.08), IL-1beta (1.43 +/- 1.13 versus 0.65 +/- 0.63 pg/ml, p = 0.03), IL-6 (9.5 +/- 6.5 versus 4.7 +/- 3.2 pg/ml, p = 0. 012), CRP (43.1 +/- 29.3 versus 23.4 +/- 25.3 mg/ml, p = 0.04), and chondrex (151.7 +/- 111.7 versus 101.4 +/- 67.3 ng/ml, p = 0.014), and increases in osteocalcin levels (14.5 +/- 5.4 versus 22.5 +/- 8. 7 ng/ml, p = 0.010) were observed. Three weeks later, the changes in N-telopeptides and osteocalcin persisted. These data indicate that pulmonary infection, through the elaboration of inflammatory cytokines, may be linked to increased bone resorption and diminished bone formation. These results provide insights into the impact of systemic inflammation on bone health, and suggest novel mechanisms for bone disease in CF.
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PMID:Adverse alterations in bone metabolism are associated with lung infection in adults with cystic fibrosis. 1106 95

This study documents values of biochemical markers of bone remodeling in 106 patients with breast cancer. Based on scintigraphic and radiological findings, patients were divided into 3 groups: 19 patients with bone metastases, 65 patients without bone metastases and normal bone scintigrams, and 22 patients with pathological, non-malignant findings on scintigraphy without proof of bone metastases. Urinary cross-linked type I collagen N-telopeptides (NTx) and serum cross-linked type I collagen C-telopeptides (ICTP) were assessed as markers of bone resorption. Bone alkaline phosphatase (BAP) was assessed as a marker of bone formation. All three markers were significantly higher in patients with bone metastases compared to both patients without skeletal recurrence and those with pathological, non-malignant scintigraphic findings (p < 0.01). There were no statistically significant differences between the latter two groups. The clinical sensitivity for diagnosing bone metastases was 44% for NTx, 65% for ICTP, and 26% for BAP, respectively. The clinical specificitiy for discriminating patients with bone disease from those without were 79%, 91%, and 92% for NTx, ICTP, and BAP, respectively. In conclusion, markers of bone remodeling are increased in patients with breast cancer metastatic to the skeleton. The sensitivity of the markers presented in this paper did not seem to be sufficient enough for early identification of patients with subclinical bone recurrence in a clinical practice setting.
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PMID:Cross-linked type I collagen C- and N-telopeptides in women with bone metastases from breast cancer. 1120 5

Adynamic bone disease and elevated serum levels of advanced glycation end products (AGEs) often are found in patients with renal failure caused by diabetic nephropathy. To clarify the role of AGEs in adynamic bone disease, we investigated the effect of these substances on cultured human osteoblasts and parathyroid cells. After 72 hours of incubation with AGEs-bovine serum albumin (BSA) (1,000 microgram/mL), there was significant inhibition of the synthesis of type I collagen and osteocalcin in response to stimulation with 10(-10) to 10(-8) M of 1,25-dihydroxycholecalciferol. In a human osteoblastic cell line (MG 63), AGEs-BSA did not affect human osteocalcin promoter activity. In human parathyroid cells, a receptor for AGEs was detected by reverse-transcriptase polymerase chain reaction. Incubation with AGEs-BSA for 48 hours significantly inhibited parathyroid hormone secretion in response to a low calcium concentration of 0.81 mM (P < 0.01). In HEK-293 cells, expressing calcium-sensing receptors, the same AGE concentration caused a significant potentiation of the extracellular Ca(2+) induced-intracellular calcium concentration after 24 and 48 hours of incubation (P < 0.05 and P < 0.01). These data suggest that AGEs are involved in the pathogenesis of adynamic bone disease by inhibiting osteoblastic activity and by inhibiting parathyroid hormone secretion in response to hypocalcemia.
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PMID:Role of advanced glycation end products in adynamic bone disease in patients with diabetic nephropathy. 1157 45

The prolonged use of retinoids has been reported to be associated with changes of bone biochemical markers and toxic skeletal effects. Among collagen markers, type I collagen N-telopeptide (NTx) is present in all tissues that contain type I collagen, mostly in bone and in cutaneous tissue. It is a reliable indicator of bone resorption in metabolic bone disease, but has not previously been investigated in dermatological diseases during retinoid therapy. Isotretinoin, a synthetic 13-cis-retinoic acid, is highly effective in the treatment of severe acne vulgaris. We evaluated the effect of low-dose short-term oral isotretinoin treatment on bone remodeling markers in 10 adolescents (mean age 17.8 years) affected by severe acne. We measured urinary NTx as a marker of bone resorption, alkaline phosphatase (ALP) and osteocalcin (OC) as markers of bone formation, parathyroid hormone (PTH) and metabolites of vitamin D (25OH-D3 and 1,25(OH)2D3). Clinical and laboratory tests were performed before and after three months of isotretinoin treatment at the dosage of 0.5 mg/kg/day. All patients showed a good clinical response to the treatment (7/10 marked improvement, 3/10 mild improvement). No changes were detected in serum PTH, 25OH-D3, 1,25(OH)2D3, OC and ALP, while urinary NTx concentrations were significantly reduced (p < 0.05). In conclusion, the lack of change in PTH, OC, ALP and vitamin D metabolites and the absence of increase of NTx suggest no bone effect of the isotretinoin treatment. The decrease of urinary NTx could be due to the effect of isotretinoin on the cutaneous component of type I collagen. Severe acne in the active inflammatory phase could change the levels of this marker. Thus, short-term low-dose oral isotretinoin is an effective and safe treatment for severe acne.
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PMID:Type I collagen N-telopeptide variation in adolescents receiving oral isotretinoin for severe acne. 1182 77

Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption. The CF subjects had moderate lung disease (FEV1: 46.1 +/- 18.6% predicted) and malnutrition (BMI: 20.0 +/- 3.3 kg/m2). Only 3 subjects had normal BMD. CF subjects had higher urinary N-telopeptides of type I collagen (81.0 +/- 60.0 vs 49.0 +/- 24.2 nm BCE/mmol creatinine, p = 0.0006) and free deoxypyridinoline (7.3 +/- 5.0 vs 5.3 +/- 1.9 nM/mM, p = 0.004) levels than controls. Serum osteocalcin levels were similar in the two groups, a result confirmed by two immunoassays that recognize different epitopes on osteocalcin. Serum bone-specific alkaline phosphatase levels were elevated in CF patients (32.0 +/- 11.3 vs 21.8 +/- 7.0 U/l, p < 0.0001), but were much more closely associated with serum total alkaline phosphatase levels (r = 0.51, p = 0.001) than with age or gender. Parathyroid hormone levels were elevated (p = 0.007) and 25-hydroxyvitamin D levels were depressed (p = 0.0002) in the CF patients in comparison with controls. These results indicate that adults with CF have increased bone resorption with little change in bone formation. Medications that decrease bone resorption or improve calcium homeostasis may be effective therapies for CF bone disease.
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PMID:Abnormal bone turnover in cystic fibrosis adults. 1190 25

Osteogenesis imperfecta (OI), commonly known as "brittle bone disease", is a dominant autosomal disorder characterized by bone fragility and abnormalities of connective tissue. Biochemical and molecular genetic studies have shown that the vast majority of affected individuals have mutations in either the COL1A1 or COL1A2 genes that encode the chains of type I procollagen. OI is associated with a wide spectrum of phenotypes varying from mild to severe and lethal conditions. The mild forms are usually caused by mutations which inactivate one allele of COL1A1 gene and result in a reduced amount of normal type I collagen, while the severe and lethal forms result from dominant negative mutations in COL1A1 or COL1A2 which produce structural defects in the collagen molecule. The most common mutations are substitutions of glycine residues, which are crucial to formation and function of the collagen triple helix, by larger amino acids. Although type I collagen is the major structural protein of both bone and skin, the mutations in type I collagen genes cause a bone disease. Some reports showed that the mutant collagen can be expressed differently in bone and in skin. Since most mutations identified in OI are dominant negative, the gene therapy requires a fundamentally different approach from that used for genetic-recessive disorders. The antisense therapy, by reducing the expression of mutant genes, is able to change a structural mutation into a null mutation, and thus convert severe forms of the disease into mild OI type I.
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PMID:Mutations in type I collagen genes resulting in osteogenesis imperfecta in humans. 1236 85


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