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PubMed1993

A patient with cardiac amyloidosis presenting a rapid increase in technetium-99m-hydroxymethylene diphosphonate accumulation.

We assessed the changes in cardiac condition in a patient with cardiac amyloidosis, by means of dual nuclei single photon emission computed tomographic (SPECT) images with technetium-99m-hydroxymethylene diphosphonate (99mTc-HMDP) and thallium-201 (201Tl). Dual SPECT showed a marked increase in myocardial 99mTc-HMDP accumulation along with deterioration of symptoms and signs, while 201Tl scintigraphy remained almost unchanged.

Aged↗
PubMed2002

Global skeletal uptake of 99mTc-methylene diphosphonate (GSU) in patients affected by endocrine diseases: comparison with biochemical markers of bone turnover.

This study aimed to clinically validate the global skeletal uptake (GSU) of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP), and to compare it with a marker of bone formation (i.e. serum osteocalcin or OC) and an index of bone resorption (i.e. urinary deoxypyridinoline or U-DPD) in different endocrine disorders affecting the skeleton. We studied 29 female patients with thyrotoxicosis (TT), 27 with primary hyperparathyroidism (PHPT), 16 with acromegaly (AC), 15 with Cushing's syndrome (CS), and altogether 110 healthy women matched for age, BMI and menstrual status. In all subjects total body digital scan images (TBDS) were acquired at 5 min and at 4 h after the administration of (99m)Tc-MDP; the whole body retention (WBR) of the tracer was measured by counting two identical sets of rectangular ROIs, and GSU was subsequently calculated by drawing an irregular ROI on 4 h TBDS images. Serum OC was assessed by IRMA and urinary DPD by fluorometric detection after reverse phase high pressure chromatography. In TT patients GSU (40.0 +/- 5.1 vs 36.5 +/- 4.8%), OC (19.1 +/- 11.8 vs 7.1 +/- 2.9 microg/l) and U-DPD (62.4 +/- 42.7 vs 19.5 +/- 5.3 pmol/pmol) were significantly ( p<0.01) higher than in controls. PHPT patients showed GSU (47.2 +/- 6.6 vs 37.8 +/- 5.3%), OC (38.6 +/- 40.9 vs 8.2 +/- 2.5 microg/l), and U-DPD (55.0 +/- 51.3 vs 21.9 +/- 6.1 pmol/pmol) values significantly ( p<0.001) higher than controls. In CS patients, GSU (39.6 +/- 6.4 vs 32.7 +/- 3.5%; p<0.01) and U-DPD (22.8 +/- 8.4 vs 16.5 +/- 2.7 pmol/pmol; p<0.05) were higher, whereas OC (3.6 +/- 2.4 vs 5.2 +/- 1.9 mg/l; p<0,05) was lower than in controls. In AC patients, GSU (34.9 +/- 5.3 vs 35.2 +/- 3.4%) did not differ significantly from controls, whereas OC (16.8 +/- 8.8 vs 6.9 +/- 2.9 microg/l; p<0.001) and U-DPD (30.9 +/- 13.6 vs 21.0 +/- 5.7 pmol/pmol; p<0.01) were higher. Stepwise multivariate linear regression analysis was performed with disease activity, creatinine clearance, age, and years since menopause as predictor variables and GSU or OC or U-DPD as dependent variables. The significant partial regression coefficients ( r) were: in TT, free triiodothyronine (fT3) with GSU ( r = 0.37; p<0.005), Ln OC ( r = 0.30; p = NS), Ln U-DPD ( r = 0.76; p<0.0001), respectively; in PHPT, PTH with GSU ( r = 0.74; p<0.001), Ln OC ( r = 0.50; p<0.05), Ln U-DPD ( r = 0.64; p<0.001); in CS Ln urinary free cortisol with OC ( r = -0.68; p<0.001) and U-DPD ( r = 0.66; p<0.05). Our data suggest that GSU could represent a valuable clinical tool for evaluating bone turnover rate in PHPT, CS, TT but not in AC. The behavior of GSU and OC and U-DPD is non-uniform in disorders characterized by a marked uncoupling between bone formation and resorption.

Acromegaly↗
PubMed2000

Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases.

The aim of this study was to determine the maximum tolerated dose of rhenium-188 hydroxyethylidene diphosphonate (HEDP) in prostate cancer patients with osseous metastases who are suffering from bone pain. Twenty-two patients received a single injection of escalating doses of carrier-added 188Re-HEDP [1.3 GBq (35 mCi), 2.6 GBq (70 mCi), 3.3 GBq (90 mCi) and 4.4 GBq (120 mCi)]. Blood counts and biochemical parameters were measured weekly over a period of 8 weeks. Haematological toxicity (WHO grading) of grade 3 or 4 was considered unacceptable. Clinical follow-up studies including methods of pain documentation (medication, pain diary) were performed for 6 months after treatment. In the 1.3-GBq group, no haematological toxicity was observed. First haematotoxic results were noted in those patients with a dose of 2.6 GBq 188Re-HEDP. In the 3.3-GBq group, one patient showed a reversible thrombopenia of grade 1, one a reversible thrombopenia of grade 2 and three a reversible leukopenia of grade 1. In the 4.4-GBq group, thrombopenia of grades 3 and 4 was observed in one and two patients (baseline thrombocyte count <200x10(9)/l), respectively, and leukopenia of grade 3 was documented in one patient. The overall nadir of thrombopenia was at week 4. The individual, maximum percentage decrease in thrombocytes in the 1.3-, 2.6-, 3.3- and 4.4-GBq groups was 17%, 40%, 60% and 86%, respectively. In two patients, a transient increase in serum creatinine was observed (max. 1.6 mg/dl). Pain palliation was reported by 64% of patients, with a mean duration of 7.5 weeks. The response rate seemed to increase with higher doses, reaching 75% in the 4.4-GBq group. It is concluded that in prostate cancer patients, the maximum tolerated dose of 188Re-HEDP is 3.3 GBq if the baseline thrombocyte count is below 200x10(9)/l. In patients with thrombocyte counts significantly above 200x10(9)/l, a dose of 4.4 GBq might be tolerable. Thrombo- and leukopenia are the most important side-effects. Pain palliation can be achieved in 60%-75% of patients receiving a dose of 2.6 GBq or more of 188Re-HEDP. Studies in a larger patient population are warranted to evaluate further the palliative effect of 188Re-HEDP.

Bone Neoplasms↗
PubMed1997

Quantification of diphosphonate uptake based on conventional bone scanning.

Up to now there has been no routinely used and easy-to-perform method for the quantification of bone uptake. Therefore, we have evaluated the clinical practicability of a new and simple method for the measurement of bone uptake based upon conventional three-phase bone scanning. In 13 patients with normal bone scans, whole-body scintigrams were obtained at 3 min and 1, 2, 3, 4, 5, 6 and 24 h after injection of 600 MBq technetium-99m hydroxymethylene diphosphonate (HMDP). Using a conventional region of interest technique, fitted time-activity curves of soft tissue and urinary excretion were established, and bone uptake was calculated from these data as the total whole-body activity minus both soft tissue activity and urinary excretion. Subsequently, the new method was tested in routine patient management: 32 healthy patients and five patients with different types of metabolic bone disease were investigated, measurements being performed only at 3 min and 3-4 h p. i. during conventional three-phase bone scanning. In the multi-imaged patient subset, soft tissue activity decreased exponentially, reaching a plateau after 6 h with a residual activity of about 14% of initial total whole-body activity. Bone uptake reached quite a stable plateau of about 27% as early as 3 h p.i., with no significant changes up to 24 h. Healthy patients of the two-scan group showed no differences in bone uptake (mean uptake values were 24.1% in women and 26.9% in men), whereas in patients with metabolic bone disease bone uptake was significantly higher, with a mean of 48% (P <0.05). Thus, the results of this method are in good agreement with the findings of standard 24-h whole-body retention measurements. The new method, however, is easy to perform, allows assessment of pure bone uptake instead of whole-body retention, and permits calculation of bone uptake by only two measurements during routine three-phase bone scanning.

Adult↗
PubMed1998

Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer.

This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine (l-T4) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer (DTC). Twenty female (14 premenopausal and 6 postmenopausal) patients receiving l-T4 suppressive therapy for DTC were studied. The sample was selected in such a way as to avoid factors influencing bone metabolism other than l-T4. All patients were monitored by sensitive thyroid-stimulating hormone, free triiodothyronine and free thyroxine assays throughout the follow-up. Nineteen healthy (12 premenopausal and 7 postmenopausal) matched women served as controls. In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99m methylene diphosphonate (GSU); bone mineral density (BMD) was measured by quantitative computed tomography at the lumbar spine (LS) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites: the femoral neck, Ward's triangle and the greater trochanter. No significant difference was found in either GSU or BMD between patients (treated for an average period of 68 months) and controls in the whole sample or in any subgroup. Furthermore, no correlations were found between either GSU or BMD and the duration of therapy, daily doses of l-T4 or results of thyroid function tests. Our data show that carefully monitored l-T4 therapy does not influence skeletal turnover (directly reflected by GSU) or the bone density of the spine and femur.

Absorptiometry, Photon↗
PubMed2001

Value of Tc-99m sestamibi scintigraphy in the detection of bone lesions in multiple myeloma: comparison with Tc-99m methylene diphosphonate.

Technetium 99m-2-methoxyisobutylisonitrile (Tc-99m MIBI) is a lipophilic agent that accumulates preferentially within living malignant cells due to the higher transmembrane electrical potential as a consequence of the higher metabolic rate than in the surrounding normal cells. It has been effectively used to detect malignant tumors at diagnosis and follow-up and has been reported to be useful in detecting disease lesions in multiple myeloma. We studied 28 consecutive patients with multiple myeloma at diagnosis to determine the value of Tc-99m MIBI in comparison with Tc-99m methylene diphosphonate (MDP), conventional X-rays, computed tomography (CT) scan, and magnetic resonance imaging (MRI). We found 26 patients with obvious osteolytic lesions in X-rays, 22 patients with positive Tc-99m MIBI scans, and 15 patients with positive Tc-99m MDP scans. There was no coincidence of the positive lesions in the two scans, while in two patients the osteolytic areas were positive in the Tc-99m MDP scans, and in one case the osteolytic area was positive in the Tc-99m MIBI scan. The intensity of Tc-99m MIBI scans correlated with disease activity as determined by lactate dehydrogenase (LDH) (p<0.05), C-reactive protein (CRP) (p<0.01), beta2-microglobulin (p<0.05), and serum ferritin (p<0.01). We believe that Tc-99m MIBI scintigraphy can detect bone marrow lesions in myeloma patients that cannot be detected by other imaging methods and that it can be useful especially in solitary myeloma to exclude other involved sites. In addition, it could be a prognostic factor related to disease activity and multidrug resistance. We believe that a multicenter study is needed to evaluate the usefulness of this agent.

Adult↗
PubMed2005

The effect of intermittent pneumatic compression on the bone uptake of (99m)Tc-labelled methylene diphosphonate in the lower limb.

INTRODUCTION: Venous compression of the lower limbs will obstruct outflow through the deep and superficial veins, yet inflow will continue, without continual swelling of the limb. It is hypothesised that venous channels in the long bones act as collateral channels to restore outflow, and therefore general blood flow through bone will increase. Such a hemodynamic change should affect the uptake of radiopharmaceuticals by the bone, though uptake changes in themselves would not definitely indicate flow changes. The purpose of this study, therefore, was to determine whether bone uptake in the lower limb is affected by intermittent venous compression, irrespective of the mechanism involved. MATERIALS AND METHODS: The effect of intermittent pneumatic compression of the thigh and calf on the uptake of (99m)Tc-methylene diphosphonate (MDP) was studied in 24 patients. All were undergoing routine bone imaging for medical conditions that were not focused on their lower limbs, and received 1 h of the therapy at 60 mmHg on one limb only, after injection of the radiopharmaceutical. Three hours after injection the relative difference in uptake (net counts per pixel) between the two limbs was calculated. The standard imaging protocol was otherwise unchanged. RESULTS: The median differences in uptake in the intermittently compressed limb compared with the contralateral limb were +7.6% (interquartile range +3.9% to +16.0%, p<0.0005 [Wilcoxon]) for the anterior aspect of the femur; +11.7% (interquartile range +4.3% to +22.2%, p<0.0005) posterior, femur; +10.5% (interquartile range +6.5% to +13.8%, p<0.0005) anterior, tibia; +10.6% (interquartile range +5.5% to +17.6%, p<0.0005) posterior, tibia. CONCLUSION: Intermittent pneumatic compression clearly and significantly increased the uptake of (99m)Tc-MDP in long bones. These data are consistent with increases in blood flow through bone, though a direct mechanical influence on the bone cannot be excluded. This effect should be given consideration during routine therapeutic and thromboprophylactic use of intermittent compression, and if the mechanism of the uptake changes can be established, their possible clinical uses should be investigated.

Adult↗
PubMed2002

Comparing whole body (18)F-2-deoxyglucose positron emission tomography and technetium-99m methylene diphosphonate bone scan to detect bone metastases in patients with breast cancer.

PURPOSE: At present, bone metastases are usually assessed using conventional technetium-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with (18)F-2-deoxyglucose (FDG-PET) can offer superior spatial resolution and improved specificity. We attempted to evaluate the usefulness of FDG-PET for detecting bone metastases in breast cancer and to compare FDG-PET results with bone scan findings. PATIENTS: The study group comprised 48 patients with biopsy-proven breast cancer and suspected of having bone metastases who underwent bone scan and FDG-PET to detect the bone metastases. The final diagnosis of bone metastases was established by operative, histopathological findings or during a clinical follow-up longer than 1 year by additional radiographs or following FDG-PET/bone scan findings showing progressive widespread bone lesions. RESULTS: A total of 127 bone lesions including 105 metastatic and 22 benign bone lesions found by either FDG-PET or bone scan were evaluated. Using FDG-PET, 100 metastatic and 20 benign bone lesions were accurately diagnosed, and using bone scan 98 metastatic and 2 benign bone lesions were accurately diagnosed. The diagnostic sensitivity and accuracy of FDG-PET were 95.2% and 94.5%, and of bone scan were 93.3% and 78.7%, respectively. CONCLUSIONS: Our findings suggest that FDG-PET shows a similar sensitivity and a better accuracy than bone scan for detecting bone metastases in patients with breast cancer.

Adult↗
PubMedDate not supplied

The effect of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on a rabbit model of athero-arteriosclerosis.

The purpose of this study was to test the effectiveness of various doses of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) in an experimental rabbit model of athero-arteriosclerosis designed by Hass et al. (Amer. J. Pathol., 49 (1966) 739). This model, which involves the feeding of a hypercholesterolemic diet in conjunction with the administration of moderately high doses of vitamin D and nicotine, results in an extensive arterial disease with complicated lesions. EHDP was administered daily by subcutaneous injection at levels of 0.25, 1.0 and 2.5 mg/kg body weight beginning with the initiation of the atherogenic regimen. Results of chemical and histopathological analyses after 8 and 12 weeks of treatment indicate the following: (1) There was a dose-related inhibition of arterial calcification at 8 weeks. At 12 weeks, only the 2.5 mg/kg dose of EHDP resulted in reduced calcification. (2) EHDP administration appeared to influence arterial lipid-containing plaque formation in medium sized arteries at 12 weeks. There was no apparent effect of EHDP administration on serum cholesterol and triglyceride levels. (3) EHDP, at a dose of 2.5 mg/kg/day, inhibited the vitamin D induced hypercalcemia. (4) EHDP administration at 2.5 mg/kg/day almost totally inhibited the thromboarteritis accompanying this disease. (5) The data thus indicate that if arterial calcification is inhibited, the other morphological effects of this treatment regime are also inhibited. This effect occurred even though serum lipid levels were unaffected. The data therefore emphasize the role of calcification in the pathogenesis of this type of experimental atherosclerosis and perhaps in human disease as well.

Animals↗
PubMed1987

The effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on necrosis of atherosclerotic lesions.

Administration of ethane-1-hydroxy-1,1-diphosphonate (EHDP) to swine with pre-established atherosclerosis resulted in lower lesion calcium concentration, smaller lesions and a decrease in the area of lesions involved in necrosis. Atherosclerosis was developed in Yorkshire swine by balloon catheter-injury to the abdominal aorta, followed by a high cholesterol-high lipid (HL) diet for 4 months. The administration of EHDP (20 mg/kg/day) was begun after these 4 months and continued for 5 additional months along with the atherogenic diet. Other swine were ballooned and fed HL diet for nine months. Morphometric analysis showed that the extent of lesions, expressed as ratio of intima to media was significantly less (P less than 0.05) in the EHDP-treated HL swine, compared to the HL diet-only group. The ratio of lesion areas showing lipid-rich necrotic debris to the area of media was also significantly smaller (P less than 0.05). Biochemical analysis showed that the lesion from the HL drug-treated group contained significantly less (P less than 0.05) calcium compared to that from the HL diet only. Finally, there was significant correlation between average lesion area and average lesion calcium concentration (P less than 0.02) for both groups. While the effect of EHDP on lesion size and calcium concentration has been previously reported for various species such as rabbit and monkey, this study is believed to be the first where a beneficial effect of EHDP on one of the most serious complications of atherogenesis - necrosis - has been documented. The mechanisms by which EHDP may affect necrosis are discussed.

Animals↗
PubMed1993

Selective elimination of macrophages by dichlormethylene diphosphonate-containing liposomes suppresses experimental autoimmune neuritis.

The injection of liposome-encapsulated dichlormethylene diphosphonate (Cl2MDP) constitutes an effective method to selectively eliminate phagocytic cells from spleen, liver and the circulation. We evaluated the effect of Cl2MDP-liposomes on the course of actively induced and adoptively transferred experimental autoimmune neuritis (EAN), both animal models of the human Guillain-Barré syndrome. Injection of Cl2MDP-liposomes 11 and 13 days postimmunization (p.i.) of Lewis rats with bovine peripheral nerve myelin efficiently prevented clinical signs of EAN up to day 15 p.i., when all control animals were affected. Thereafter, EAN gradually also developed in Cl2MDP-liposome-treated rats, but until day 19 disease was significantly milder than in control rats injected with buffer-filled liposomes. Adoptive transfer EAN (AT-EAN) induced by injection of activated P2-specific T cells could be suppressed even more markedly by application of Cl2MDP-liposomes 1, 3, and 6 days after cell transfer. Efficient suppression of AT-EAN by Cl2MDP-liposomes rules out the possibility that EAN is prevented due to interference with the induction phase of this experimental disease and confirms that macrophages are important effector cells during EAN. Selective suppression of phagocytic cell function by drug-containing liposomes may hold promise as a novel treatment of demyelinating autoimmune diseases of the nervous system.

Animals↗
PubMed1991

Assessment of bone remodeling in the temporomandibular joint by serial uptake measurement of technetium 99m-labeled methylene diphosphonate with a cadmium telluride probe.

Regional uptake of technetium 99m-labeled methylene diphosphonate was measured serially over time to follow the healing course of surgically generated lesions, induced unilaterally in the condyles of beagles. A small portable cadmium telluride probe was used for radiation detection, with and without a gold collimator attached. Radioactivity was measured at six periarticular sites on both the operated and the contralateral control sides and expressed as a ratio with respect to a reference site over the sagittal suture. The use of a collimator was crucial to separate the activity associated with bone mineralization in the condylar head from that arising in the adjoining bones. The uptake in the condylar region increased 2 weeks after surgery and remained at a constant level above the presurgery baseline (p less than 0.05) until termination of the study (10 weeks). Postmortem histologic examinations confirmed the high bone turnover level by revealing newly formed bone as well as the presence of osteoclasts. The time course of nuclide uptake in the temporomandibular joint is different from the general pattern of rise and fall of activity displayed in other bones and indicates the persistence of bone remodeling processes during a prolonged period of at least 10 weeks.

Adult↗
PubMed1991

Studies on focal alveolar bone healing with technetium (Tc)-99m labeled methylene diphosphonate and gold-collimated cadmium telluride probe.

The benefit of using a collimator for a miniaturized cadmium telluride probe was evaluated by monitoring the bone-healing processes for 13 weeks after the induction of small iatrogenic alveolar bone lesions in one side of the mandible in beagles. Technetium (Tc)-99m labeled methylene diphosphonate (200 to 300 MBq, 5.1 to 8.1 mCi, in a solution of 0.5 to 1 ml, intravenously) was used as a bone-seeking radiopharmaceutical. The radioactivity over the bone lesion (L) and the contralateral normal site (C) in the mandible were measured between 1.5 and 2 hours after injection of the tracer, and the activity ratio L/C served as an index of relative bone uptake. A study of six dogs revealed that the healing response to a hemispheric bone defect of 2 mm diameter in the cortical bone could not be detected by an uncollimated probe, and in a repeated study in two dogs the use of a gold collimator (5 mm in diameter, 5 mm in length) did not increase the L/C ratio significantly. A second study in six dogs with 5 mm lesions showed that although systematic trends in the time courses of the L/C ratio obtained both with and without the collimator could be demonstrated, the L/C ratio of collimated versus uncollimated measurements was significantly (p less than 0.005) increased. In three of the latter six dogs, abscesses developed after 9 weeks, leading to a second increase (p less than 0.05) of the L/C ratio with collimation compared with the noninflammation group; without collimation no significant (p greater than 0.15) difference between the two groups could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Process↗
PubMed1994

Effects of liposome-encapsulated dichloromethylene diphosphonate on macrophage function and endotoxin-induced mortality.

Dichloromethylene diphosphonate (Cl2MDP), encapsulated into liposomes, is known to eliminate splenic and hepatic macrophages. In the present study we investigated the time course of the effects of i.v. injected Cl2MDP-liposomes on macrophage function in rats from 2 h to 14 days postinjection. We further assessed the impact of Cl2MDP-liposomes on endotoxin-induced lethality. Magnetometry was used to measure uptake and distribution of magnetic particles in different organs and to non-invasively monitor cell organelle motion and disappearance of particles in Kupffer cells. Cl2MDP-liposomes administered to rats pre-injected with magnetic particles, resulted in a biphasic impairment of the cell organelle motion after 1 h and 48 h. At 8 h, retained particles started to leave the liver, indicating the begin of an irreversible damage to hepatic macrophages. The released magnetic material was redistributed and taken up primarily by spleen and bone marrow. Pretreatment with Cl2MDP-liposomes for 24 h and 48 h significantly depressed phagocytic capacity for magnetic particles in Kupffer cells. Again, this was compensated by an increased uptake by spleen, lungs, and bone marrow. Interestingly, i.v. administration of endotoxin after pretreatment with Cl2MDP-liposomes resulted in a significant reduction in mortality from 55% to 14%.

Animals↗
PubMed1981

Effects of ethane-1 hydroxy-1, 1-diphosphonate (5 mg/kg/day dose) on quantitative bone histology in Paget's disease of bone.

The effects of ethane hydroxy diphosphonate (EHDP) on quantitative bone histology have been studied in 43 pagetic patients treated for 6 months at a dose of 5 mg/kg/day. To determine the therapeutic effects on pagetic bone and to appreciate the side effects in non-pagetic bone, the patients were biopsied either in pagetic or non-pagetic areas of the ilium before the beginning of the treatment and at 3, 6 and 9 months (i.e. 3 months post-therapy) after the inception of treatment. Tetracycline double labelling of bone was performed before biopsies in each patient to measure the calcification rate. The results demonstrate that 5 mg/kg/day EHDP given for 6 months has a marked antiosteoclastic effect which is prolonged after the cessation of treatment. Pagetic osteoclasts appear more sensitive to EHDP than normal osteoclasts. The new bone formed during treatment has a regular lamellar texture. At the same time, the high appositional rate of pagetic bone is reduced to a normal value. Marrow fibrosis is reduced along with the reduction in the osteoclast population. Thus, pagetic bone changes to bone normal in quantity, quality and metabolism. Dynamically, in nonpagetic areas, a transitory decrease of calcification rate is noted at the end of the treatment, without morphological evidence of osteomalacia, except for 2 out of 43 cases. Histologically, EHDP given at a dose of 5 mg/kg/day for 6 months appears to be an effective and safe treatment for Paget's disease of bone.

Adult↗
PubMed1982

Effects of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) in adult normal and selectively parathyroidectomized rats. I. Effects on plasma calcium, bone tissue, and adrenal glands at low or normal calcium intake.

One-year-old intact and selectively parathyroidectomized rats were given a normal or low calcium diet for 8 months and, during the last 3 weeks, diphosphonates (EHDP) at a low dose level of 1.0 mg EHDP/kg body weight/day intraperitoneally. The administration of EHDP impaired the animals' ability to maintain the blood calcium level during a low calcium intake. Calcium-deficient intact animals had significantly reduced plasma calcium during EHDP treatment, while calcium-deficient parathyroidectomized animals showed no further reduction. Calcium deficiency alone resulted in osteoporosis which was prevented by parathyroidectomy. The short period of EHDP treatment had no significant effect on the bone mass in control, osteoporotic, and parathyroidectomized animals. The calcium accretion rate by bone became significantly increased upon a low calcium intake in intact rats but not in parathyroidectomized ones. This increase was counteracted by EHDP which gave rise to reduced accretion in both parathyroidectomized and osteoporotic animals. In addition EHDP caused hypertrophy of the adrenal cortex in all treated groups.

Adrenal Glands↗
PubMed1981

Assessment of synthetic steroid (Org OD 14): effect on skeletal metabolism by 24-h whole-body retention of diphosphonate.

Using a 24-h whole-body retention (WBR) of Tc99m hydroxyethylidene diphosphonate (HEDP), a sensitive measure of skeletal metabolism, 24 women receiving the synthetic steroid hormone Org OD 14 were studied. OD 14 was found to have a powerful suppressive effect on skeletal metabolism in both oophorectomized and non-oophorectomized women when compared with control subjects (P less than 0.001 and P less than 0.01, respectively). The degree of suppression was similar to that found with oestrogen therapy. While it has previously been shown that OD 14 prevents bone mineral loss (as measured by photon-absorptiometry), the present study provides further evidence as to the efficacy of this compound in suppressing skeletal metabolism.

Alkaline Phosphatase↗
PubMed1986

Reversed-phase HPLC of 99mTc methylene diphosphonate bone imaging kits with quantification of pertechnetate.

Ion-pairing reversed-phase HPLC is used to separate a mixture of 99mTc methylene diphosphonate (MDP) complexes prepared by tin reduction of pertechnetate in the presence of ligand. Chromatographic conditions allow for the quantification of total pertechnetate concentration, as well as the determination of chemical purity of generator eluents from which 99mTc is derived. Both determinations can be made prior to actual labeling. Commercially available MDP kits from three manufacturers are evaluated. All three MDP kits, when labeled with 99mTc, produce multiple, chromatographically separable components. The formation of these Tc-MDP complexes is time dependent. The labeling procedure produces several products within the first 20 min, with up to fifteen complexes observed after 4 h. The results of this work demonstrate the presence of substantial chemical contamination in generator eluents.

Bone and Bones↗