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PubMed2004

Comparison of whole-body STIR-MRI and 99mTc-methylene-diphosphonate scintigraphy in children with suspected multifocal bone lesions.

The study was performed to compare whole-body short time inversion recovery (STIR) MR imaging and (99m)Tc-methylene diphosphonate planar scintigraphy in the examination of children with suspected multifocal skeletal malignant lesions. Sixteen patients with known or suspected malignant skeletal disease underwent both whole-body STIR MR imaging and bone scintigraphy. The lesions were described and numbered according to scintigraphic evaluation criteria. Thus, 16 regions were analyzed in each patient for the comparison between the two modalities. Histology was proven in the primary malignant regions. Follow-up MRIs were registered. Scintigraphy and MRI follow-up were evaluated as gold standard. A total of 139 different lesions was observed by both modalities. Baseline whole-body MRI revealed 119 bone lesions in 256 possible sites (46.5%); scintigraphy revealed only 58 lesions (22.6%). Congruence was observed in only four patients (25%). According to the location of the lesion, correlation was observed in 39/139 lesions (28%). In all, 57.5% of the lesions were detected only by MRI and 14.5% of the lesions were detected only by scintigraphy. Whole-body MRI was more sensitive (P<0.001). Of all lesions numbered which could be separated in the initial MRI, whole-body MRI detected 178 lesions in the patients. The results suggest that whole-body MRI using a STIR sequence is an effective radiation free method for examination of children with suspected multifocal bone lesions. MRI showed more lesions than conventional (99m)Tc-methylene diphosphonate scintigraphy. Therefore, whole-body MRI may be feasible as a screening modality for metastatic and skip lesions in osteosarcoma, PNET, Ewing sarcoma and Langerhans cell histiocytosis in children.

Adolescent↗

PubMed1995

Uptake and biodistribution of 99mtechnetium methylene-[32P] diphosphonate during endosteal healing around titanium, stainless steel and hydroxyapatite implants in rat tibial bone.

Early evaluation of intraosseous implant success and failure is critical, but, until now, there have been no reliable systems of measurement. The present study assessed whether the use of 99mtechnetium methylene-[32P]diphosphonate (99mTcMD32P), a marker for both bone formation and mineralization, can indicate if an implant is bone-bonding or non-bonding. Moreover, this study examined how bone-bonding (titanium and hydroxyapatite) and non-bonding (stainless steel) implants affected the normal healing of bone after marrow ablation, as measured by uptake of 99mTc and 32P. Titanium, hydroxyapatite and stainless steel implants were placed in the right tibiae of Sabra strain rats following ablation of the marrow, and 99mTcMD32P was injected 18 h before harvest. AT 3, 6, 14, 21 and 42 d (and in some experiments, on days 28 and 35) post-injury, the treated and contralateral tibiae were removed and cleaned of soft tissue. The uptake of 99mTc and 32P was measured in the whole bone, as well as in its organic and inorganic phases. Effects of the implants were assessed by comparing the treated to the untreated tibia in each rat. The distribution of 99mTc and 32P varied with each implant. After the insertion of titanium, increased 99mTc uptake was seen in whole bone and in the inorganic and organic phases at days 6-14. 32P uptake in whole bone and in the inorganic phase increased only at day 6, and 32P uptake was decreased in the organic phase at that time. In tibiae implanted with hydroxyapatite, 99mTc and 32P uptake was seen in the whole bone at days 6 and 14. While 99mTc uptake was increased in both the organic and inorganic phases, 32P uptake into the organic phase was decreased at both day 6 and day 14. In tibiae implanted with stainless steel, effects were observed only on day 6. The increased 99mTc uptake in whole bone reflected increases in both the organic and mineral phases. Increased 32P uptake was observed in whole bone as well, due to an increase in the 32P uptake in the mineral phase only; incorporation of 32P in the organic phase was comparable to that found in the contralateral limb. The results of this study indicate that implants alter bone healing, as indicated by the uptake of 99mTc and 32P in the different bone compartments. Moreover, decreased 32P uptake by the organic phase in the presence of bone-bonding implants suggests that cleavage of 99mTcMD32P into its technetium and methylene diphosphonate moieties was inhibited, perhaps as a function of the onset of calcification in the newly synthesized osteoid. The effect of the implants on bone healing was observed on days 6-14, when active bone formation and mineralization were occurring, supporting the hypothesis that these materials events associated with initial calcification. Uptake of 99mTc varies as a function of time, and uptake of 32P varies with time and distribution in the mineral or organic phase of bone, suggesting that these parameters may be useful as indicators of bone-bonding.

Animals↗

PubMed1990

The investigation of osteoradionecrosis of the mandible by 99mTc-methylene diphosphonate radionuclide bone scans.

The need for a reliable non-invasive investigation in osteoradionecrosis (ORN) of the mandible is discussed. The results of 99mTc-methylene diphosphonate bone scans using single photon emission tomography, and measuring dynamic uptake in 13 patients are presented. These suggest that sites of osteoradionecrosis may be defined by a paradoxically increased uptake of 99mTc-methylene diphosphonate.

Gamma Cameras↗

PubMed1992

Soft-tissue localization of 99mTc-hydroxymethylene diphosphonate due to interaction with calcium.

Soft tissue localization of 99mTc-labelled bone imaging agents is often associated with high calcium levels either locally or systemically. This could be due to the formation of a large molecular complex after administration of the radiopharmaceutical. We have investigated the formation of such a complex between 99mTc-hydroxymethylene diphosphonate (HMDP) and calcium by a number of techniques. The results indicate that 99mTc-HMDP is a colloidal preparation which may contain particles up to 280 nm in size, and that the labelled colloid may aggregate in the presence of calcium salts forming particles up to 3 microns. Such particles are too large to permit free diffusion across vascular epithelium but large enough to localize in the liver or lungs. It is suggested that this interaction may be responsible for soft tissue localization of the technetium-labelled bone imaging agents. In vivo the radiolabelled complex in a mixture of 99mTc-HMDP and calcium chloride localizes to a significantly larger extent in liver, spleen and muscle and less in bone compared with 99mTc-HMDP diluted with saline. The increased liver and spleen uptake can be prevented by prior administration of non-radioactive colloid but this does not significantly improve the bone uptake of the 99mTc-HMDP/calcium chloride mixture. The clinical relevance of these findings lies in their possible explanation for soft-tissue uptake and poor bone accumulation of the technetium-labelled diphosphonates in some patients. This may be particularly important in evaluating quantitative bone scans, especially if serial scanning is done to monitor disease progress or therapy since local or systemic calcium levels may change between scans.

Animals↗

PubMed2006

Two new hybrid organic/inorganic copper(II)-oxovanadate(V) diphosphonates: [Cu2(phen)2(O3PCH2PO3)(V2O5)(H2O)] x H2O and [Cu2(phen)2(O3P(CH2)3PO3)(V2O5)] x C3H8. Synthesis, structure, and magnetic properties.

Two new hybrid organic/inorganic copper oxovanadium diphosphonates [Cu2(phen)2(O3PCH2PO3)(V2O5)(H2O)] x H2O (1) and [(Cu2(phen)2(O3P(CH2)3PO3)(V2O5)] x C3H8 (2) have been obtained by hydrothermal synthesis. The compounds are monoclinic, and they crystallize in the space group P2(1)/n with cell parameters of a = 11.788(2) A, b = 17.887(3) A, c = 14.158(2) A, and beta = 93.99(0) degrees and in the space group C2/c with cell parameters of a = 11.025(1) A, b = 18.664(2) A, c = 15.054(2) A, and beta = 90.06(0) degrees, respectively. Both compounds present two-dimensional frameworks built up from infinite chains of corner-sharing vanadium tetrahedra and diphosphonate groups connected by copper tetramers for (1) and copper dimers for (2). The remarkable feature of (2) is the encapsulation of propane molecules, stabilized by strong hydrogen bonding between the layers. The magnetic properties of the compounds have been investigated showing antiferromagnetic coupling with Tmax = 64 K for (1) and Curie-like paramagnetic behavior for (2).

Journal Article↗

PubMed1981

Tubular handling of phosphate along the nephron of thyroparathyroidectomized rats injected with ethane-1-hydroxy-1,1-diphosphonate.

1. Previous studies have shown that in thyroparathyroidectomized rats injection of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at doses that inhibit bone mineral retention (0.16 mmol = 10 mg of phosphorus/kg body wt. per day subcutaneously) leads to a decrease in the net tubular reabsorption of phosphate. 2. In the present work the tubular response to EHDP (0.16 mmol/kg body wt.) injected subcutaneously for 9 days has been localized by free-flow micropuncture in thyroparathyroidectomized rats. 3. The results show tht the net tubular reabsorption of phosphate along the first portion of the (early) proximal tubule was markedly depressed in the EHDP-injected thyroparathyroidectomized rats compared with that in the pair-fed thyroparathyroidectomized control animals. In this latter group the delivery of phosphate to the distal tubule was larger than in the final urine, confirming previous reports. In the EHDP-injected thyroparathyroidectomized rats no difference in delivery of phosphate was found between the distal tubule and the final urine, suggesting that diphosphonate inhibited net reabsorption of phosphate in the terminal nephron. 4. The sites of the EHDP-induced changes in the tubular handling of phosphate were similar to those previously determined for the adaptive response to an increase in the supply of phosphate.

Animals↗

PubMed1979

Sacro-iliac joint scanning with technetium-99 diphosphonate.

Quantitative sacro-iliac (SI) joint scanning with methylene diphosphonate labelled with technetium-99 (99TcMDP) was performed in 25 control patients, in 16 patients with definite ankylosing spondylitis, in 23 patients with mechanical low back pain, and in 12 patients with seronegative arthritis. The mean radio-isotope index in the control group was 1.2 +/- 0.15. The highest value was 1.5. Values in excess of 1.5 were seen in patients with clinically active ankylosing spondylitis but not those with inactive disease. Three of the 12 seronegative arthritis patients (without clinical or radiological evidence of sacro-iliitis) had elevated values: all of these were positive for HL-A B27. An important finding was that six of the 23 patients with mechanical or non-specific low back pain had values above 1.5, unassociated with B27. These data emphasize the need for caution in the interpretation of abnormal sacro-iliac scans. Radio-isotope bone scanning can provide a qualitative and quantitative assessment of inflammatory activity in joints with minimal radiation exposure. Various authors have shown its value in providing early evidence of sacro-iliitis (Russell et al., 1975; Namey et al., 1977). In this study, methylene diphosphonate labelled with technetium-99 (99TcMMDP) has been used to produce quantitative sacro-iliac scans in order to evaluate sacro-iliac disease in four groups of patients presenting with or without low back pain.

Arthritis↗

PubMed2001

Ethane-1,2-diphosphonic acid as a building block in supramolecular chemistry; a pillared-layer framework and framework-encapsulated cations.

The 1:1 adduct of piperazine and ethane-1,2-diphosphonic acid is a salt [C(4)H(12)N(2)](2+).[C(2)H(6)O(6)P(2)](2-), in which both ions lie across centres of inversion in space group P2(1)/c. The anions are linked by a single type of O-H...O hydrogen bond [O...O, 2.562 (3) A; H...O, 1.73 A, O-H...O, 169 degrees ] into (6, 3) nets built from a single type of R(4)(4)(22) ring. The cations lie between these nets, linked to them by two types of N-H...O hydrogen bond [N...O, 2.635 (3) and 2.735 (3) A; H...O 1.72 and 1.82 A, N-H...O, 175 and 177 degrees ] such that the cations link adjacent sheets, thus forming a pillared-layer framework. The aquated adduct formed between trimethylenedipiperidine and ethane-1,2-diphosphonic acid is also a salt [C(13)H(28)N(2)](2+).[C(2)H(6)O(6)P(2)](2-).2.8[H(2)O], in which there are 12 different types of hydrogen bond, eight O-H...O and four N-H...O. The anions are linked into chains by pairs of O-H...O hydrogen bonds and these chains are linked by the water molecules into a continuous three-dimensional framework. Within the anion/water framework are large voids which contain pairs of cations, linked to the framework by N-H...O hydrogen bonds.

Journal Article↗

PubMed1983

Pathologic fracture due to severe osteomalacia following low-dose diphosphonate treatment of Paget's disease of bone.

Ethane-I-hydroxy-I,I-diphosphonate (EHDP) 5 mg/kg body weight/day was administered to a patient suffering from Paget's disease of bone. After 150 days of treatment, when the plasma alkaline phosphatase was 40% of initial, he suffered a pathologic fracture of his Pagetic right patella, which was found to have osteomalacia of extreme severity. An iliac crest bone biopsy, following double tetracycline labels, also showed severe osteomalacia of Pagetic bone. Osteoclast acid phosphatase activity was reduced, as occurs in diphosphonate-treated rats. The patient's history included two previous pathologic fractures of Pagetic bone and unusual sensitivity to EHDP. It might be prudent to perform needle bone biopsy in order to exclude osteomalacia in EHDP-treated patients with these clinical manifestations.

Etidronic Acid↗

PubMed1984

Some pharmacological and biochemical interactions of the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate with the guinea-pig urinary bladder.

Adenosine 5'-triphosphate (ATP) and adenylyl 5'-(beta, gamma-methylene)-diphosphonate (AMP-PCP) both contracted the guinea-pig urinary bladder, but the response to AMP-PCP was much greater. We synthesized the enantiomer of AMP-PCP, L-adenylyl 5'-(beta, gamma-methylene)-diphosphonate (L-AMP-PCP), and tested it on the guinea-pig bladder. L-AMP-PCP contracted the guinea-pig bladder, and was more potent than AMP-PCP and much more potent than ATP. The potential breakdown product of L-AMP-PCP, L-adenosine, unlike adenosine (the breakdown product of AMP-PCP), did not inhibit contractions of the guinea-pig bladder. ATP and its enantiomer L-adenosine 5'-triphosphate (L-ATP) were rapidly degraded by the muscle, and AMP-PCP was also degraded, but more slowly. L-AMP-PCP, however, was completely resistant to degradation. L-AMP-PCP would appear to be a useful ATP analogue, as it is potent and resistant to degradation, and its potential breakdown product, L-adenosine, is inactive.

Adenosine↗

PubMed1978

The effects of ethylene-1-hydroxy-1, 1-diphosphonate on cellular transformation and organic matrix of the epiphyseal growth plate of the rat--a light microscopic and ultrastructural study.

Ethylene-1-hydroxy-1, 1-diphosphonate (EHDP) was administered intraperitoneally to one-day-old rats. In the first experiment, each animal was given 4 injections of EHDP distributed over two consecutive days and corresponding to a total amount of EHDP of 100 mg/kg bwt/day. The animals were sacrificed 12 hours after the last injection. In the second experiment, each animal was given 3 injections, each containing 50 mg of EHDP/kg bwt, with an interval of 6 hours and were thereafter left to survive for 4 days. Animals in the first experiment showed in comparison to normal controls an increased width of the hypertrophic zone; lack of calcified septa within the zone of provisional calcification; persistent atypical chondrocytes in the calcification zone and a large number of matrix vesicles lacking in crystals. The ground substance showed an accumulation of fine precipitates apparently representing undegraded aggregates of proteoglycan macromolecules. Animals in the second experiment formed a new apparently normal epiphyseal growth plate, while the "old" epiphyseal cartilage formed under the influence of EHDP remained largely unresorbed within the metaphysis. Besides the previously described inhibitory effects of diphosphonates on the crystallization of matrix vesicles and the growth of hydroxyapatite crystals, EHDP, at the doses used, was found to have a profound inhibitory effect on the differentiation and migration of the epiphyseal chondrocytes as well as on the degradation of proteoglycan macromolecules. The observed inhibition of vascular invasion appears to be related to inhibition of enzyme degradation of the ground substance, as evidenced by the observation of extracellular lysosomelike bodies in the erosion zone.

Animals↗

PubMed1969

Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo.

Two diphosphonates containing the P-C-P bond, CH(3)C(OH)(PO(3)HNa)(2) and H(2)C(PO(3)HNa)(2), inhibit the crystallization of calcium phosphate in vitro and prevent aortic calcification of rats given large amounts of vitamin D(3). The diphosphonates therefore have effects similar to those described for compounds containing the P-O-P bond but are active when administered orally.

Animals↗

PubMed1992

Treatment of pulmonary alveolar microlithiasis with a diphosphonate--preliminary results of a case.

A diphosphonate, disodium etidronate, a compound known to inhibit microcrystal growth of hydroxyapatite was given to a 3.5-year-old girl with pulmonary alveolar microlithiasis (PAM) that was symptomatic. The drug was used for approximately 36 months in a single daily dose of 15 mg/kg. No significant side effects were encountered with somewhat clearing of lung bases in chest radiograms and subjective improvement in general condition. These findings suggest a role of diphosphonates in the treatment of PAM.

Calcinosis↗

PubMed1978

A technique for measuring the accumulation of 99 Tcm stannous-ethane-1-hydroxy-1, 1-diphosphonate in the canine tibia.

An experimental technique is described to measure the accumulation of 99Tcm-stannous-ethane-1-hydroxy-1, 1-diphosphonate (99Tcm-EHDP) in the canine tibia. The method involves infusion at a constant rate of known amounts of 99Tcm-EHDP into the nutrient artery supplying the tibial bone. The accumulation of the diphosphonate in bone is measured by an external sodium iodide, Nal (T1), scintillation detector. Results are presented showing that for small amounts of 99Tcm-EHDP (0.004-0.300 mg per hour) the accumulation is a nearly linear function with time for 60 minutes, after which the uptake may become variable with either a plateau formation or considerable fluctuation of activity.

Animals↗

PubMed1974

The value of Tc99m-diphosphonate (HEDSPA) as a skeletal scanning agent.

A new "bone seeking" agent, namely the organic compound diphosphonate labeled with Tc99m was tried in 21 patients for skeletal scanning. In 3 cases, although the clinical and roentgenographic evidence of bone lesions was absent, bone metastases were found, and these were confirmed histologically. The organic diphosphonate is more stable compared to the inorganic polyphosphates and the images obtained are excellent.

Animals↗

PubMed1992

Evaluation of finger blood flow with Tc-99m MDP (methylene diphosphonate).

BACKGROUND: A variety of methods were used to establish objective diagnostic criteria of Raynaud's phenomenon. We intended to introduce another method, using radionuclide (Tc-99m methylene diphosphonate) scintigraphy, which is more objective, simple and economical than the past methods. METHODS: The finger blood flow with radionuclide scintigraphy was evaluated in 10 patients of Raynaud's syndrome, 12 patients of connective disease without Raynaud's symptoms, and 20 normal persons. After immersing one hand in ice water (4 degrees C) for 30 seconds, the hand was exposed to 22 degrees C room air for 15 minutes, and then the patients received the intravenous (IV) bolus of 20 microCi of Tc-99m methylene diphosphonate (MDP). At the same time, scintigraphic image of both hands started with the region of interest, including the second, third, fourth and fifth fingers distal to the metacarpophalangeal (MCP) joints. Computer recording of the counts in the region of interest every 2 seconds for 310 seconds was started on IV bolus injection. RESULTS: The 310 seconds cumulative digital blood flow ratio of cold exposed hand to room air exposed hand was significantly lower in Raynaud's group (p < 0.001), and the ratio of initial slope of activity curve was also lower in the Raynaud's group (p < 0.001). Of the 8 patients showing Raynaud's syndrome, 4 patients of scleroderma and 1 patient of multiple myeloma showed no improvement of finger blood flow in the cold exposed hand after 2 weeks of pharmacological therapy, but 1 patient of mixed connective tissue disease, 1 patient of Behcet's syndrome and 1 patient of SLE showed much improved finger blood flow after combined administration of vasodilator, calcium channel blockers and antiplatelet drugs. CONCLUSIONS: The evaluation of finger blood flow with 99mTc-MDP could be considered to be one of the simple, economical and new methods that can be used in the follow-up, objective assessment of therapeutic effect, and giving an aid in the study of the pathophysiology of the Raynaud's phenomenon.

Adult↗

PubMed1989

[Differential diagnosis of osteomalacia and other forms of renal osteodystrophy in terminal renal failure by dynamic scintigraphy with diphosphonate].

During osteomalacia in patients with terminal renal failure, the coefficient of diphosphonate elimination from the blood bed (K1) was less than 0.1 min-1, which was determined by the rise of the concentration of uremic toxins, inhibiting interaction of the radiopharmaceutical with the bone, in the patients' tissues. Dynamic scintigraphy permits one to study the pharmacokinetics of diphosphonate in every patient and thus can be used for differential diagnosis between osteomalacia and other forms of renal osteodystrophy.

Chronic Kidney Disease-Mineral and Bone Disorder↗

PubMedDate not supplied

[Effect of diphosphonates on bone tissue of the rat during hypokinesia].

The diphosphonate effect on bones was studied in Wistar male rats weighing about 200 g. The rats were kept for 60 days in small-size cages where their motor activity was diminished. Every day the rats were given per os 0.3% solution of 1-hydroxy-ethylene-1,1-diphosphonate (HEDP) containing 9 mg/kg phosphorus. In the course of hypokinetic exposure the rats developed generalized osteoporosis. Histomorphometric measurements demonstrated that the drug did not prevent mineral losses from the tubular bones (humerus, femur). However, the drug led to a complete bone mass recovery in the pelvic and a partial recovery in the sternum. The drug also produced a preventive effect on the population of cells-precursors of osteogenesis the number of which decreases significantly during hypokinesia.

Animals↗