Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study has examined the effect of prostate cancer on bone matrix formation and mineralisation by osteoblasts, with special reference to osteomalacia. Sixty-seven patients with prostatic bone metastases underwent transiliac bone biopsy after double tetracycline labelling. Histomorphometric analysis was then undertaken in areas distant from, local to and infiltrated by prostate cancer. In bone free of tumour (n = 45) and bone surrounding metastases (n = 7) both matrix formation and corrected mineral apposition rate were low. By comparison osteoid surface, osteoid volume and mineral apposition rate were markedly increased within metastases (tumor-free bone vs. metastatic bone, p < 0.0001), a finding consistent with a high bone turnover state. Although osteoblast function was disturbed both within metastases and in tumour-free areas, classical osteomalacia was not associated with prostate cancer.
 ...
PMID:Osteoblast function and osteomalacia in metastatic prostate cancer. 837 52

The majority of the patients with advanced prostate carcinoma have painful skeletal metastases, which are responsible for significant skeletal morbidity and disability. Most of these metastases are osteosclerotic, but it has been shown that the abnormal osteoblastic bone formation within metastases is preceded by osteoclastic activation, which appears to be associated with bone pain. This provides the rationale for using bisphosphonates, which are powerful and selective inhibitors of osteoclastic bone resorption. Several bisphosphonates have been shown to be clinically useful for the treatment of several conditions characterized by abnormal osteoclastic bone resorption, including Paget's disease, primary hyperparathyroidism, myelomatosis, and skeletal metastases. Its efficacy in relieving pain in patients with skeletal metastases due to prostate carcinoma has been confirmed in a few studies. The bisphosphonate clodronate was extensively investigated in the study unit. When infused intravenously i.v. (300 mg/day) relief of bone pain become appreciable within 3 days, sometimes preceded by a transient pain flare. These clinical results are very consistent and the residual pain usually is of extraosseous origin. Thus, with regard to pain of strictly bone origin, unresponsive patients are quite rare. Oral administration also is effective, but due to its limited intestinal absorption the effective dose is on the order of 1600-3200 mg/day. These doses usually are well tolerated, but they may be a problem for severely ill patients. Furthermore, the efficacy of treatment becomes apparent only after a few days. Thus, oral clodronate usually is adopted as a continuation of an i.v. course. The duration of the i.v. therapy should be individualized, but usually the more prolonged the treatment the longer the duration of the effect. For practical reasons, clodronate is infused daily for 5 days (Monday-Friday) and the treatment course is repeated at the time of any significant recurrence. The oral continuation prevents or delays the recurrence of bone pain in most patients, but in some patients this therapy has to be integrated occasionally with i.v. infusion. The duration of the effect for the same bioavailable dose is somewhat related to the degree of malignancy of the primary tumor. In an uncontrolled study, the author also evaluated the effectiveness of alendronate given either i.v. or orally. A single infusion of 5 mg alendronate i.v. produces roughly the symptomatic effect of 5 i.v. infusions of 300 mg clodronate. Alendronate, 40 mg orally/day, was effective in reducing bone pain in 11 of 12 patients with bone metastases due to prostate carcinoma but who were not confined to bed. In some patients with prostate carcinoma and a diffuse metastatic invasion of the skeleton, there is indirect biochemical and histologic evidence of osteomalacia. This can be aggravated by bisphosphonate administration because of the transient striking prevalence of osteoblastic activity over bone resorption, which also occasionally causes the appearance of symptomatic hypocalcemia. Therefore, the use of large oral supplements of calcium is recommended, particularly at the start of therapy. It is conceivable that these calcium supplements also may be able to improve the final clinical outcome of the bisphosphonate therapy. In conclusion, administration of large doses of bisphosphonates is one of the most cost-effective palliation treatments for patients with prostate carcinoma with bone metastases, both as first-line therapy and in the long term. With appropriate doses, a large proportion of patients can be maintained free of bone pain until death. Studies of the ability of lower doses to prevent skeletal morbidity in patients without metastases or with asymptomatic bone lesions are warranted.
 ...
PMID:Bisphosphonates in prostate carcinoma. 936 35

Since bone markers may reflect different aspects of bone disorders and cell function, and osteolytic and osteoblastic activities may be individually or concomitantly altered, determination of more than one marker type is generally appropriate. Also, the individual markers of a particular type do not necessarily show parallelism. For example, in osteomalacia from vitamin D deficiency, bone-specific alkaline phosphatase may be grossly elevated because of enhanced osteoblastic activity, whereas the vitamin D dependent osteocalcin may be decreased. With the exception of measurement of the bone enzymes, bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase, bone marker measurements require complex and expensive immunoassays. As a general rule, the simple enzyme measurements can precede other investigation in most bone disorder> Bone-specific alkaline phosphatase measurement alone is generally adequate for the investigation of osteomalacia, Paget's disease and hyperparathyroidism but should be combined with measurement of tartrate-resistant acid phosphatase in suspected metastatic disease, and in multiple myeloma. Determination of both enzymes together may also be of value in the investigation of osteoporosis but in this disorder added benefit may be obtained by the addition of other bone markers, particularly urine deoxypyridinoline and possibly serum collagen telopeptide.
 ...
PMID:Biochemical markers of bone turnover. 974 51

We report a male patient who presented with suspicion of skeletal metastases based upon an abnormal 99-mTc bone scan, which showed increased uptake at both femoral heads, left femoral neck, and several ribs. The images also suggested reflex sympathetic dystrophy, subcapital fracture of the left femur, and rib fractures. A diagnosis of hypophosphataemic osteomalacia was finally made.
 ...
PMID:Reflex sympathetic dystrophy in hypophosphataemic osteomalacia with femoral neck fracture: a case report. 1081 79

We report a case of an 80-year-old man with osteoblastic metastases from advanced carcinoma of the prostate presenting with a grand mal seizure resulting from severe hypocalcaemia. He had low serum phosphate and ionised calcium levels, elevated serum skeletal alkaline phosphatase and intact parathormone levels. 99mTc radioisotope bone scan revealed a "super bone scan" suggestive of osteomalacia. The serum 1, 25-dihydroxycholecalciferol level was unexpectedly elevated. The biochemical abnormalities persisted despite high dose calcium replacement, but improved with supraphysiological doses of 1,25 (OH)2 vitamin D3 (Rocaltrol) therapy. We hypothesise that the hypocalcaemia in this patient was due to vitamin D resistance secondary to a humoral factor secreted by the tumour.
 ...
PMID:A man with osteoblastic metastasis and hypocalcaemia. 1106 7

There is a spectrum of presentations of skeletal manifestations of malignancy that includes generalized osteopenia and hypercalcemia, focal osteolysis, focal osteogenesis, and osteomalacia and hypophosphatemia. In various preclinical animal models, parathyroid hormone-related protein (PTHrP) was seen to be produced by tumor cells, causing osteolytic lesions, either with or without hypercalcemia. EB1089, an analog of 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3], when used as a potential therapeutic agent, decreased both the number and size of metastatic bone lesions, the incidence of hind limb paralysis, and the volume of tumor burden within the bone, and also prolonged survival time. These findings were attributed to the interruption of pathways leading to PTHrP production. From studying osteoblastic metastases of prostate cancer in preclinical animal models, urokinase expression by the tumor was proposed as a growth factor and as an activator of other bone growth factors; however, the mechanism of action of osteoblastic metastases requires further research. The design of suitable preclinical animal models to study the pathophysiology of oncogenic osteomalacia also needs further investigation, though a genetic model of hypophosphatemic osteomalacia exists. The animal models and study designs used all establish methodologies that can be adapted for use in future clinical trials.
 ...
PMID:Extending preclinical models of skeletal manifestations of malignancy to the clinical setting. 1154 70

We present the case of a 42 year old man, with a history of multiple fractures and generalized pain for two years. A three phase bone scan, demonstrated multiple fractures involving the ribs, both ankles and feet. After going through a battery of tests which included an FDG PET scan (to exclude an occult malignancy), the patient was diagnosed with osteomalacia and hyperparathyroidism. The FDG PET scan, demonstrated multiple foci of increased FDG uptake throughout the axial skeleton, in a pattern highly suggestive of pseudofractures, rather than osseous metastases.
 ...
PMID:[FGD PET in a patient with pseudofractures from osteomalacia]. 1182 Oct

Neoplasms, with or without metastases in bones, can induce pathological bone remodeling, leading to systemic bone resorption and hypercalcemia or osteomalacia and normocalcemia. The aim of the present study was to investigate the effect of a cytostatic--cyclophosphamide on the skeletal system in rats. The experiments were carried out in male Wistar rats with initial body weight of 212-229 g, divided into 3 groups (n = 6): I--Control, II--Cyclophosphamide (10 mg/kg m.c. i.m. daily for 14 days, and after a 7-day break, for 7 days), III--Cyclophosphamide (20 mg/kg m.c.p.o. daily for the initial 14 days). After 30 days of the experiment, the animals were killed and bone mass, length and diameter of long bones, mineral content in bones, transverse cross-section surfaces of the cortical diaphysis and of the marrow cavity, transverse growth, width of endosteal and periosteal osteoid in the tibia, width of trabeculae, width of epiphyseal cartilage and mechanical features of the femur were examined. Cyclophosphamide caused disorders of bone tissue remodeling. Decreases in bone mass, length, diameter, mineral content in bones, width of trabeculae in the femur, transverse growth, width of osteoid, transverse cross-section surface of the cortical diaphysis, and worsening of mechanical properties of the femur were observed.
 ...
PMID:[Effect of cyclophosphamide on bone remodeling in rats]. 1459 73

We report the case of a severe symptomatic hypophosphatemic osteomalacia in a 66-year-old patient with hormone-refractory prostate cancer metastatic to the skeleton. A follow-up of 2 years from diagnosis to development of hormone refractoriness and death allowed us to study the natural history of this uncommon disturbance of mineral homeostasis in this common malignancy. Relevant to the difficult management of the late stages of prostate cancer is the failure of hypophosphatemia to respond to conventional therapeutic approaches and the favorable outcome of antitumor therapy suggesting that this group of patients, although having a poor prognosis, could still benefit from aggressive second line therapy. In this malignancy in which metastases have a predilection for bone, failure to recognize osteomalacia can only result in significantly increasing the burden of skeletal complications.
 ...
PMID:Severe hypophosphatemic osteomalacia in hormone-refractory prostate cancer metastatic to the skeleton: natural history and pitfalls in management. 1566 96

Patients harboring cancer and other tumors frequently exhibit such bone morbidity as metabolic bone diseases and bone metastases. Cancers produce and secrete cytokines and growth factors for their growth and survival. Cytokines are also produced by reacting immune systems. Those humoral factors, when produced in a sizable quantity, enter into the general circulation and become a causative principle for paraneoplastic syndrome. An example is parathyroid hormone-related protein (PTHrP) for humoral hypercalcemia of malignancy, and fibroblast growth factor 23 (FGF23) for oncogenic osteomalacia. In animal models, PTHrP appear to produce cancer-associated cachexia as well. Some particular cancers such as those of lung, prostate, breast and thyroid are prone to metastasize into bone resulting in metastatic bone disease. Interactions between these cancers and inhabitant bone cells and bone matrices constitute a favorable condition where particular cancer cells deposit and survive. A variety of principle factors, mostly signal materials, were identified that are responsible for these interactions and these principle factors can be a target for the development of new chemotherapeutic agents.
 ...
PMID:[Bone in malignant disorders: introduction]. 1658 3


<< Previous 1 2 3 4 5 Next >>