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)

The presented case-history demonstrates an infant with a rare bone disease with a very serious prognosis. Based on X-ray findings on the skeleton (sclerosis of the diaphyses of long bones, ribs, vertebrae and in particular the base and vault of the skull), the diagnosis of morbus Camurati-Engelmann--progressive diaphyseal dysplasia was established. With regard to the striking progression of the process in the cranial area and the progressing stigmatization of the patient's face, the authors consider also a more recent diagnostic unit--craniodiaphyseal dysplazia. With advancing sclerotization of the skull the most serious complications are compression of the cranial nerves which can be resolved in the final stage only by surgery. From a brief review of the literature: the aetiology of the disease is not known, the therapeutic effect of prednisone or calcitonin is small.
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PMID:[The Camurati-Engelmann syndrome (progressive diaphyseal dysplasia)]. 180 71

We have conducted an open, prospective study to investigate the efficacy of a single 60 mg infusion of pamidronate as alternative therapy in 15 subjects with severe Paget's bone disease refractory to calcitonin. Disease activity was assessed with a visual-analogue score of symptom severity, plasma alkaline phosphatase and quantitative estimation of 99mTc-methylene biphosphonate uptake on bone scan. All indices of disease activity fell after pamidronate, reaching a nadir at 3 months. Although disease activity increased thereafter, only 3 subjects required retreatment within 12 months. Plasma calcium fell after 3 days and remained below baseline levels for 6 months associated with evidence of secondary hyperparathyroidism. Pamidronate was well tolerated; femoral neck fractures occurred in 2 subjects with severe local Paget's disease but were unlikely to be due to the drug. We conclude that pamidronate is an effective and promising alternative for treatment of patients with severe Paget's disease no longer adequately controlled by calcitonin. Calcium supplementation may be prudent to prevent secondary hyperparathyroidism associated with the use of this agent.
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PMID:Single-dose intravenous pamidronate is effective alternative therapy for Paget's disease refractory to calcitonin. 181 3

Osteoclasts were isolated from membranous bone from four children without metabolic bone disease who were undergoing craniotomy for either tumor or trauma. Both freshly isolated osteoclasts and those cultured for 4-7 days exhibited the following characteristics: production of tartrate-resistant acid phosphatase (9.5-14.8 units), contraction in response to application of 100 mg/ml of human calcitonin, and formation of resorption lacunae on devitalized bone wafers. Nuclear estrogen and progesterone receptors were demonstrated by immunohistochemical techniques and quantitated in two of the patients by radioimmunoassay (estrogen receptor RIA, 23.6 and 23.8 cpm/micrograms protein; progesterone receptor RIA, 36.7 and 74.2 cpm/micrograms protein). The demonstration of sex steroid hormone receptors in the nucleus of osteoclasts derived from children with normal membranous bone has established a potential mechanism whereby direct modulation of bone resorption by the sex steroid estrogen and progesterone may occur.
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PMID:Osteoclasts isolated from membranous bone in children exhibit nuclear estrogen and progesterone receptors. 223 65

In a multicentre open trial 530 patients suffering from primary osteoporosis, secondary osteoporosis and Sudeck's disease were enrolled to assess synthetic human calcitonin efficacy on bone pain relief. Spontaneous pain, pain on movement, provoked pain, functional impairment and patient's assessment were recorded. During the first 30 days of treatment, all the parameters significantly improved (p less than 0.01) and the tolerability was satisfactory. Four hundred and ten patients entered a follow-up study, this number gradually decreasing over a 6-month period due to a satisfactory outcome. Efficacy on bone pain remained very high in most of the patients, many of whom continued to improve. These results suggest that synthetic human calcitonin is highly effective on pain and functional impairment in bone disease and is well tolerated.
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PMID:Human calcitonin in the management of osteoporosis: a multicentre study. 241 7

The pathogenesis, clinical features, indications for therapy, and current pharamacologic management of Paget's disease are reviewed. Paget's disease is a bone disorder of unknown etiology primarily affecting the elderly. Overactive bone resorption leads to the accelerated formation of disorganized, weak bone. Pain and fractures are common clinical features. Neurologic, cardiovascular, metabolic, and neoplastic complications are also reported. Because most patients are asymptomatic, the disease is often detected during routine roentgenography or laboratory tests. Primary indications for pharmacologic intervention include bone pain, neural compression, immobilization hypercalcemia or hypercalciuria, cardiac failure, and orthopedic surgery. Recurrent or non-healing fractures and rapidly progressing complications are additional indications. Drugs used in the management of Paget's disease include calcitonin, etidronate disodium, and plicamycin. Although these agents are efficacious, each has disadvantages. Clinical resistance to animal calcitonins may develop, and the cost of therapy may be prohibitive. Etidronate may induce ostemalacia. The use of plicamycin is limited by potentially severe toxicities. Dichloromethylene and aminohydroxypropylidene are promising diphosphonate compounds but are still investigational In those patients who are unresponsive to single-agent regimens, combination therapy may prove effective. Although many patients with Paget's disease do not require pharmacologic therapy, calcitonin and etidronate are the agents of choice when it is indicated.
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PMID:Pharmacologic management of Paget's disease. 266 12

Osteocalcin (OC), also called Bone Gla Protein (BGP), is a bone matrix protein of 5800 MW synthesized by osteoblasts. Since OC is mainly metabolized in the kidney, its blood concentration is altered in renal failure. The relationship between OC and the calcium-phosphorus regulating hormones (parathyroid hormone, calcitonin) and the biochemical parameters of bone metabolism (serum calcium, serum phosphorus and serum alkaline phosphatase) was studied in 30 patients on chronic hemodialysis (mean age: 51 years; mean duration of dialysis treatment: 39 months). OC levels were significantly elevated in all patients on chronic hemodialysis (34.7 +/- 31.5 ng/ml) when compared to healthy subjects (6.25 +/- 1.39 ng/ml, p less than 0.001). In 2 patients the OC levels were excessively high (127.54 ng/ml; 148.02 ng/ml), which was associated with severe renal osteodystrophy due to secondary hyperparathyroidism. When divided into 2 groups in the patients with secondary hyperparathyroidism the mean OC value was markedly elevated (50.5 +/- 12.7 ng/ml) compared to the patients without secondary hyperparathyroidism (24.1 +/- 2.8 ng/ml) (p less than 0.05). 70 per cent of the patients on chronic hemodialysis with OC levels greater than 30 ng/ml showed moderate to severe scintigraphic findings of bone disease. In neither of the 2 groups could a correlation between OC and serum alkaline phosphatase be demonstrated. The results indicate, that OC levels could be useful additional parameter in hemodialyzed patients with secondary hyperparathyroidism and OC levels could reflect bone formation in these patients.
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PMID:[Osteocalcin in chronic hemodialysis patients as an additional parameter in the diagnosis of advanced secondary hyperparathyroidism]. 278 25

It appears that at present, serum BGP is the one bone protein that has the most promise for assisting in the diagnosis and management of high turnover metabolic bone disease states. If further studies confirm its usefulness in osteoporosis as a predictor of rapid bone loss without the need for bone biopsy, this serum marker will then not only allow early detection but also an appropriate choice of therapy in osteoporosis, i.e. the use of specific inhibitors of high turnover states such as estrogen, calcitonin, or bisphosphonates. In addition, it may also permit more accurate follow-up of patients suffering from diseases such as primary hyperparathyroidism after surgery. In low turnover osteoporosis, it may also serve a useful function to observe whether the osteoblast can be stimulated to enhance bone formation with therapies such as fluoride, anabolic steroids, PTH, etc. As yet, additional measurements, such as bone histomorphometry and other bone mineral markers, are required for definitive diagnosis. Hopefully, the availability of specific well-characterized antibodies against BGP may define its role more accurately. Recently, several other new bone proteins have been identified but at present they have very limited clinical application. Future studies into the structure-function relationship of these bone proteins may identify those markers which will be most relevant to the diagnosis and treatment of metabolic bone disease.
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PMID:Serum and urinary markers of bone remodeling: assessment of bone turnover. 306 73

Response to acute and chronic administration of calcitonin and calcium and of biphosphonates (EHDP) was evaluated in 14 patients with Paget's bone disease who were grouped on the basis of homogeneous disease activity, as appraised by bone involvement and alkaline phosphatase and hydroxyproline levels. At first, 100 MRC U of calcitonin followed 4 hours later by 500 mg of elemental calcium were given for 10 days; a significant (p less than 0.001; paired and unpaired Student t test) reduction in alkaline phosphatase (-25%) and hydroproline (-55%) was observed. Subsequently, 5 mg/kg/day of EHDP was given for 20 days. Both parameters increased to levels similar to basal values. These increases were significant (p less than 0.001 for the paired and unpaired Student test) compared with those obtained after calcitonin administration; alkaline phosphatase rose +27% and hydroxproline +135%. After this, patients were divided into 2 groups (A and B). Group A was treated with calcitonin and calcium, at the dosage indicated above, for 10 days a month during 6 months. Group B continued with the same protocol with the addition of EHDP for the 20 days during which calcitonin and calcium were not given. The results of 6 months of treatment showed that calcitonin was more active and suggested that EHDP diminishes hormonal effects. These results also demonstrate a short-term absence of EHDP activity.
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PMID:Biochemical assessment of acute and chronic treatment of Paget's bone disease with calcitonin and calcium with and without biphosphonate. 313 91

An 8-year-old boy with idiopathic juvenile osteoporosis and multiple fractures had three abnormalities of bone mineral metabolism: calcitonin deficiency, elevated serum calcitriol concentrations, and hypercalciuria. Calcitonin deficiency was documented by two attempts to stimulate calcitonin secretion with intravenous calcium and pentagastrin. Treatment for 11 months with daily subcutaneous injections of human calcitonin and oral administration of calcitriol failed to reduce the excessive bone resorption observed on bone biopsy, and the fracture rate did not decrease. Treatment was discontinued for two months, then resumed with calcitonin injections and oral calcium supplementation. The fracture rate decreased but bone biopsy continued to show excessive resorption. Therapy was discontinued. After the onset of puberty, endogenous calcitonin was detectable. Exogenous calcitonin therapy may have failed to control bone resorption for several reasons: insufficient dose, reduction of bone receptors from long-term calcitonin exposure, secondary hyperparathyroidism, or lack of association between calcitonin deficiency and the bone disease.
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PMID:Effect of calcitonin replacement therapy in idiopathic juvenile osteoporosis. 317 35

Paget's disease is a relatively common bone disease. This review aims to present reasonable treatment recommendations with enough background to understand them. To accomplish this end, some aspects of basic bone cell biology, biochemistry, and pathology are presented, as are speculations about possible causes of this disease. Treatment of Paget's disease will be considered in three sections. The first two sections will review treatment with calcitonin and diphosphonates, respectively. These sections briefly will consider the mechanism of action of the drugs, review in detail clinical studies of drug effectiveness, and summarize the advantages and disadvantages of each drug. The third section details specific treatment recommendations for each of the six clinical settings in which treatment of Paget's disease is justified.
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PMID:Paget's disease of bone. 327 10


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