SEARCH · PubMed Health

Results for “Diphosphonates”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed1985

Results of the administration of diphosphonate for the prevention of heterotopic ossification after total hip arthroplasty.

We evaluated the results in 177 patients with 200 total hip arthroplasties that had been performed for primary osteoarthritis. Severe postoperative heterotopic-bone formation (grades III and IV according to the classification of Brooker et al.) was found in thirty-six hips (18 per cent). The incidence of heterotopic bone formation was found to be slightly higher in the patients who had received diphosphonate than in the control group of patients who had received either a placebo or no drug therapy. The postoperative range of motion of the hips as well as ratings for pain, walking, and function did not differ significantly between the treated and untreated groups. The results of this study were consistent with those of previously published reports that demonstrated that while diphosphonates did not prevent heterotopic bone formation in laboratory animals they did result in a delay of mineralization of osteoid. This delay did not, as was hoped, significantly improve the range of motion of the involved hips in our series.

Clinical Trials as Topic↗

PubMed1983

Relative distribution of diphosphonate between bone and soft tissue at 4 and 24 hours: concise communication.

Digital bone scintigrams were obtained in 19 patients using Tc-99m hydroxyethylidene diphosphonate (HEDP). These were quantitated for skeletal, soft-tissue and renal uptake of tracer using a contrast-enhancement technique to define the regions of interest. Twenty-four hr whole-body retention (WBR) of HEDP was also measured. It was found that approximately 70% of retained diphosphonate was localized in the skeleton at 24 hr, with 26% in soft tissue and 4% in kidneys. However, we have shown that over a wide spectrum of whole-body retention measurements (18 to 70%) the 24-hr soft-tissue component, as a percentage of administered dose, remained relatively constant whereas skeletal tracer accumulation mirrored WBR (r = 0.98, p less than 0.001). The present study indicates that, despite a significant but essentially stable soft-tissue component, measurement of 24-hr WBR of HEDP accurately reflects skeletal metabolism.

Bone and Bones↗

PubMed1984

[Congenital angular deformity of the tibia in chick embryo induced by ethane-1-hydroxy-1, 1-diphosphonate (EHDP)].

Congenital angular deformity of the tibia (CADT) is one of the classic inborn errors. The treatment of the disease is very difficult because of insufficient clinical and experimental data and lack of complete experimental model of the disease. The present study is designed to establish a new experimental model of CADT. In vivo experiment: Only one injection of ethane-1-hydroxy-1,1-diphosphonate (EHDP) (4 X 10(-2)-4 X 10(-1) mumol/g egg wt.) was given into the yolk sac of fertile white leghorn egg at 8 days of incubation. The skeletal deformities of the chick embryos were examined during the period of EHDP-administration until hatching. Furthermore, the effect of EHDP was compared with that of its analogs (dichloromethylene diphosphonate: Cl2MDP and inorganic pyrophosphate: PPi) in a similar manner. In vitro experiment: Tibiae from 9-day-old chick embryos were cultured at 37 degrees C for 6 days by roller-tube method in the medium containing EHDP, Cl2MDP or PPi at concentrations of 4-400 microM to measure dry weight and calcium content of the tibiae. The results are summarized as follows. Angular deformity of the tibia in chick embryo was produced in vivo specifically by EHDP-administration compared to its analogs. There existed the critical stage of bone development and the critical dose of EHDP-administration to induce angular deformity of the tibia. The incidence and the severity of the tibial bowing depended on the dose of EHDP-administration. The thinning of periosteal bone collar and retardation of primary bone marrow formation were observed in EHDP-administered tibia. According to 3H-thymidine autoradiographic study, EHDP inhibited DNA synthesis of osteoblast by about 58% after 2 days of administration. The DNA synthesis of chondrocyte was also inhibited by about 20% after 2 days of EHDP-administration. EHDP had a more inhibitory effect on calcification of chick embryonic tibiae than Cl2MDP and PPi at concentration of 40 microM without influencing the dry weight of tibiae in vitro. This new experimental model of CADT offers a significant possibility to elucidate the etiology of this disease.

Abnormalities, Drug-Induced↗

PubMed1981

[Inhibitory action of diphosphonate on the development of pancreatic concrements (experiment with EHDP (author's transl)].

The application of the diphosphonate EHDP (ethane-I-hydroxy-I,I-diphosphonate) prior to the commencement of a calciphylactic experiment (SELYE) inhibits the interstitial calcification and fixation of apatite in the pancreas of female rats (dosage: 20 mgEHDP i. p. per 150 g body mass). Thus the inhibitory potency of EHDP on soft tissue calcification is confirmed. Previously, on the basis of experimental results, a therapeutic administration of this substance in the field of clinical pancreatology could not be derived because the most of human intraductal calculi is composed of calcium carbonate.

Animals↗

PubMed1996

Repopulation of murine Kupffer cells after intravenous administration of liposome-encapsulated dichloromethylene diphosphonate.

Kupffer cells were selectively eliminated in mice by the intravenous administration of liposome-entrapped dichloromethylene diphosphonate. At 5 days, small peroxidase-negative and acid-phosphatase-weakly-positive macrophages appeared, increased in number, and differentiated into peroxidase- and acid-phosphatase-positive Kupffer cells. Repopulating small macrophages actively proliferated, and the number of Kupffer cells returned to the normal level by day 14. The numbers of macrophage precursors in the liver as detected by the monoclonal antibodies ER-MP20 and ER-MP58 increased after liposome-entrapped dichloromethylene diphosphonate injection. ER-MP58-positive cells proliferated and differentiated into ER-MP20-positive cells and eventually into BM8-positive Kupffer cells in the liver. Bone-marrow-derived ER-MP58-positive cells were also detectable in the liver and differentiated into ER-MP20-positive cells, but they did not become BM8-positive macrophages. Macrophage colony-stimulating factor mRNA expression was enhanced in the liver 1 day after injection. The administration of macrophage colony-stimulating factor did not shorten the period of Kupffer cell depletion but increased the number and the proliferative capacity of repopulating Kupffer cells. These findings implied that repopulating Kupffer cells are derived from a macrophage precursor pool in the liver rather than from bone-marrow-derived monocytes. Local production of macrophage colony-stimulating factor in the liver plays a crucial role in the differentiation, maturation, and proliferation of Kupffer cells.

Animals↗

PubMed1980

Spinal meningeal uptake of technetium-99m methylene diphosphonate in meningeal seeding by malignant lymphoma.

Definite diagnosis of meningeal seeding by systemic cancer relies on the presence of malignant cells in the cerebrospinal fluid (CSF). In the absence of such cells in the CSF, only two other tests strongly suggest the diagnosis--a CT scan and a myelogram. We report a case in which the diagnosis was strongly suggested by an unusual uptake of Tc-99m methylene diphosphonate by the leptomeninges during a skeletal scan and later established by the presence of malignant cells in the CSF. We believe that radionuclide scan may be an additional diagnostic test in some cases with meningeal seeding by systemic cancer. We therefore are extending our studies to validate this possibility.

Aged↗

PubMed1988

Effects of diphosphonate and x-rays on bone lesions induced in rats by prostate cancer cells.

Prostate adenocarcinoma-III (PA-III) cells deposited over the scapula of Lobund-Wistar (L-W) rats induced osteolytic and osteoplastic changes in that bone. The osteolytic process was prevented and interrupted by administrations of dichloromethylene diphosphonate (Cl2MDP); but the osteoplastic process, once initiated, continued. The latter process was interrupted by ionizing radiation. Treatments of PA-III-affected bones with Cl2MDP and x-rays immobilized both osteolytic and osteoplastic processes.

Adenocarcinoma↗

PubMed1989

Single high-dose (45 mg) infusions of aminohydroxypropylidene diphosphonate for severe malignant hypercalcemia.

A 3-hour single intravenous infusion of aminohydroxypropylidene diphosphonate (APD) 45 mg was given to 25 patients with malignant hypercalcemia. There were seven patients with breast cancer, eight with lung cancer, and ten with a variety of other cancers. Twenty-four patients responded to a single APD 45 mg infusion, 18 of whom (75%) had falls in plasma calcium to below the upper limit of normal (less than or equal to 2.75 mmol/l). Of 15 patients who had severe hypercalcemia, i.e., plasma calcium levels greater than 3.5 mmol/l, 14 responded and 9 (60%) achieved normocalcemia. Five patients developed hypocalcemia. One patient with lung cancer developed spontaneously reversible acute dyspnea after APD which was considered to be an idiosyncratic drug reaction. Single short-duration infusions of APD 45 mg are very effective in correcting malignant hypercalcemia in the majority of patients and are particularly suitable for patients with pre-APD plasma calcium levels greater than 3.5 mmol/l, who are less likely to develop hypocalcemia.

Adult↗

PubMed1979

The effect of dichloromethylene diphosphonate, a pyrophosphate analog, on bone and bone cell structure in the growing rat.

Dichloromethylene diphosphonate (Cl2MDP) is a synthetic compound related in structure to inorganic pyrophosphate but is resistant to enzymatic and chemical degradation and is known to be a potent inhibitor of bone resorption. The administration of 20 mg/kg/day of Cl2MDP for ten days to growing rats results in marked increases in metaphyseal mineralized tissue mass due to slowed bone resorption. There was an increase in resorption areas covering anorganic bone viewed by scanning electron microscopy (SEM), however, the resorption pits, or Howship's lacunae, in these resorption areas were smaller and less defined than those encountered in controls. The appearance of these large areas of poorly delineated resorption pits is likely due to an inhibition of bone resorption coupled with slow bone formation. Administration of Cl2MDP to growing rats also results in an increase in the numbers and size of osteoclasts. Because this would appear to be a histological paradox, in view of the ability of Cl2MDP to slow bone resorption, the osteoclasts were examined by transmission electron microscopy (TEM). The ruffled borders and associated cytoplasmic vacuoles were generally less extensive in the Cl2MDP-treated osteoclasts than in controls, even though clear zones were frequently seen. Examination of undecalcified light microscope sections reveal that the area of bone being degraded by adjacent osteoclasts was generally much smaller in the Cl2MDP-treated animals than in controls. Thus the collaborating TEM observations of smaller ruffled borders, with the SEM observations of smaller, less-defined resorption pits, with the light microscope observations of smaller bone areas being degraded by individual osteoclasts provide a morphological basis for the observed decreases in bone resorption following Cl2MDP administration.

Animals↗

PubMed1988

An evaluation of serum osteocalcin in Paget's disease of bone and its response to diphosphonate treatment.

We found that serum bone gamma-carboxyglutamic acid-containing protein (BGP) (osteocalcin) had lower sensitivity and specificity for measurement of disease activity in Paget's disease of bone than other biochemical measures of disease activity. The administration of diphosphonates induced suppression of urinary hydroxyproline excretion and a subsequent decrease in alkaline phosphatase values, but no consistent change in BGP values. Serum BGP measurements have limited value as a screening test for Paget's disease or for monitoring treatment of the disorder.

Alkaline Phosphatase↗

PubMedDate not supplied

Normal pharmacokinetics of 99mTc-diphosphonate after intravenous administration.

In the past several years bone imaging has become a routine diagnostic tool for the nuclear medicine clinician. However, increased information may be derived by determining the ratio-pharmacokinetic parameters associated with blood, urine, and bone. In an adult male population of normals (N = 5--6) blood clearance, urinary excretion, and skeletal uptake of 99mTc-Diphosphonate were determined as a function of time after intravenous (i.v.) administration. The quantitative imaging studies (lower lumbar region) were performed up to 1 h post administration with a scintillation camera interfaced to a computer. Blood levels exhibited a triexponential clearance pattern and urinary excretion of the radiopharmaceutical was essentially complete by 4 h. The computer-generated images showed an initial early uptake in bone, kidneys, and soft tissue. Thereafter, a parallel fall-off in activity was observed in kidneys and soft tissue, with a concomitant increase in bone.

Adult↗

PubMed1987

Aminohexane diphosphonate in the treatment of Paget's disease of bone.

We studied the effects of the intravenous or oral administration of aminohexane diphosphonate (AHDP) in 42 patients with active Paget's disease of bone. Treatment of mouth (400 mg daily for 1 month) or intravenously (25 mg or 50 mg daily for 5 days) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 39 and 42% of pretreatment values (oral and IV treatments respectively), and was followed by a similar decrease in the serum activity of alkaline phosphatase. In both groups of patients, disease activity remained suppressed for the 6 months of followup, and pain improved in 34 out of 37 patients who had bone pain attributed to Paget's disease. Both biopsies indicated that osteoblast and osteoclast numbers decreased with no adverse effects on mineralization. Neither regime was associated with significant side effects. We conclude that short courses of AHDP provide a promising treatment for the long-term control of Paget's disease.

Administration, Oral↗

PubMed1989

Three-phase [99mTc]diphosphonate scintimetry in septic and nonseptic arthritis of the immature knee: an experimental investigation in dogs.

We compared the informative value of dynamic and static [99mTc]diphosphonate ([99mTc]DPD) scintimetry in early septic arthritis (SA) and chronic nonseptic arthritis (NSA) of the knee in puppies. SA (n = 10), induced by injection of Staphylococcus aureus into one knee, was examined after 48 h. NSA (n = 6) was induced by weekly intraarticular instillation of 1% carrageenan and examined at 2 and 12 weeks. Epiphyseal and metaphyseal count ratios (CRs) between experimental and control joint were calculated in an angiographic phase (0-20 s), a "blood pool" phase (20-256 s), and a bone uptake phase (2 hs). Control dogs (n = 4) had a CR of 1.0 in all regions and phases, the coefficients of variation being 0.06 and 0.03 in dynamic and static phases, respectively. In NSA, all scintimetric phases showed decreased metaphyseal uptake and largely unchanged epiphyseal uptake. Generally, SA exhibited vastly increased angiographic uptake in all regions and increased epiphyseal blood pool uptake, whereas delayed epiphyseal uptake varied and delayed metaphyseal uptake tended to decrease. Two septic joints had generalized reduction in dynamic uptake, probably owing to increased intraarticular pressure; in one of these, dynamic uptake in the distal femoral epiphysis (FE) was totally absent, suggesting temporary circulatory arrest during the dynamic scanning procedure. The use of regional dynamic and static [99mTc]DPD scintimetry increased the pathophysiologic and diagnostic value of joint scintigraphy, especially with respect to the early detection of SA and its avascular complications.

Animals↗

PubMed1992

[99mTc]diphosphonate uptake and hemodynamics in experimental arthritis: effect of naproxen in the canine carrageenan injection model.

The impact of naproxen treatment on juxta-articular hemodynamics and bone metabolism in experimental juvenile arthritis was studied in the articular carrageenan injection model. Unilateral gonarthritis was induced for 12 weeks in eight dogs receiving naproxen (dosage, 2 mg/kg) and eight controls. Regional blood flow was assessed by the microsphere method, plasma volume by the distribution space of [125I]fibrinogen, and bone metabolism by the 2-h uptake of [99mTc]diphosphonate ([99mTc]DPD). Synovial effusion was less prominent with naproxen treatment as judged by joint fluid volume and pressure. Naproxen reduced the arthritic capsular hyperemia, almost normalized a severe blood flow increase in patella and both juxta-articular epiphyses, ameliorated an expansion of plasma volume in the patella and the distal femoral epiphysis, and normalized an increased [99mTc]DPD uptake in subchondral femoral bone and the tibial cortex. Significantly increased arteriovenous shunting in the arthritic extremity was unaffected by naproxen. The study suggests that long-term cyclooxygenase inhibition offers protection against hemodynamic and metabolic changes in juxta-articular bone secondary to synovial inflammation.

Animals↗

PubMed1984

Acute intravenous infusion of disodium dihydrogen (1-hydroxyethylidene)diphosphonate: mechanism of toxicity.

The acute intravenous toxicity of disodium dihydrogen (1-hydroxyethylidene)diphosphonate (etidronate disodium; I) and the mechanism of this toxic response have been investigated in 40 beagle dogs. The intravenous toxicity of I is dependent on the total dose administered and the length of the infusion interval. The toxicity of I is directly related to the ability of the drug to bind or complex with the circulating calcium in the blood. Maximum depressions in ionized calcium coincide in time with peak blood levels of I, and at lethal doses electrocardiographic changes indicative of hypocalcemia are observed. For a 2-min infusion of 2 mg of I/kg, no effect is observed on ionized calcium levels, and the electrocardiogram remains normal. At doses of 16 and 32 mg/kg, coincident with an immediate fall in ionized calcium levels, there is a transient rise in total calcium and a fall in phosphorus levels. The ionized calcium level rises, and total calcium level falls and stabilizes at baseline levels within 30 min after the infusion. However, the phosphorus level rises and exceeds the baseline value, reaching 3-4 times normal by 72 h after the infusion. With proven lethal doses of I (60 mg/kg infused over 2 min) and the simultaneous infusion of an ionized calcium salt such as calcium gluconate (20 mg of Ca2+/kg), electrocardiograms remain normal and death is prevented. Thus, an effective antidote in the event of an overdose or too rapid an infusion of I can be employed to prevent acute toxic effects.

Anesthesia↗

PubMed1988

Prevention of calcification of bioprosthetic heart valve leaflets by Ca2+ diphosphonate pretreatment.

Calcification frequently causes failure of bioprosthetic heart valves (BHV) fabricated from glutaraldehyde-pretreated porcine aortic valve or bovine pericardium. Systemic diphosphonate therapy inhibits this disease process, but with adverse effects on overall growth, bone development, and calcium metabolism. The present study was designed to examine the hypothesis that the immobilization of ethanehydroxydiphosphonate (EHDP) within BHV as the poorly soluble Ca2+ salt would inhibit calcification at drug levels insufficient to produce side effects. Glutaraldehyde-pretreated pericardial BHV tissue was exposed to a physiologic concentration of Na2EHDP (0.14 M in 0.05 M HEPES, pH 7.4) and subsequently washed in a NaCl or CaCl2 (0.14 M in 0.05 M HEPES, pH 7.4) solution to precipitate the Na or Ca2+ salts of EHDP on/within the tissue, respectively. Incorporation of CaEHDP into BHV ranged from 74.8 nM/mg (after 1 h, 37 degrees C) to 353 nM/mg (2 weeks, 22 degrees C). None of the Na2EHDP was incorporated into BHV without exposure to CaCl2. In vitro release of CaEHDP from BHV into a physiologic buffer not containing Ca2+ was rapid, with greater than 95% removed after 4 d, while release of CaEHDP into buffer containing a physiologic concentration of Ca2+ ion (1.5 mM) was markedly reduced, with 30% of the precipitated CaEHDP remaining immobilized on or within the tissue matrix following 21 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

The beneficial effects of diphosphonate and piroxicam on the osteolytic and metastatic spread of rat prostate carcinoma cells.

Transplantable rat prostate adenocarcinoma III cells produce local tumors and osteolytic and osteoplastic lesions and they metastasize through defined lymphatic channels to the lungs in which they produce expanding focal tumors. The bone lesions were prevented by treatments with dichloromethane diphosphonate (Cl2MDP). Treatment of rats with piroxicam, a nonsteroidal antiinflammatory drug, suppressed to some extent tumor growth, bone destruction, and metastasis. However, simultaneous treatments of rats with both drugs (Cl2MDP and piroxicam) prevented bone damage and suppressed tumor growth and metastatic spread very significantly without evidence of toxicity.

Adenocarcinoma↗

PubMed1983

Effect of dichloromethylene diphosphonate (Cl2MDP) on immune function in breast cancer patients with bone metastases.

Immune function was studied in normocalcemic breast cancer patients with bone metastases treated with either dichloromethylene diphosphonate (Cl2MDP) or placebo. The results showed no significant difference between the two patient groups. This suggests that Cl2MDP does not markedly impair the host's defense mechanisms, and in this respect can be safely used in the treatment of patients with resorptive bone disease.

Adult↗