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PubMed1984

Bone tissue in Paget's disease treated by ethane-1, hydroxy-1, 1 diphosphonate (EHDP). Structure, ultrastructure, and immunocytology.

Diphosphonates have been used in the management of Paget's disease of bone because of their experimentally demonstrated antiosteoclastic activity. Light microscopic examination of bone tissue from 13 patients with Paget's bone disease who were receiving (EHDP) treatment showed considerably reduced osteoclastic resorption accompanied by gradual replacement of irregular woven bone by lamellar tissue. Electron microscopic examination confirmed that pagetoid osteoclasts are morphologically abnormal cells and degenerate after EHDP treatment. EHDP does not affect the measles nucleocapsid-like inclusions in the osteoclast nuclei. Immunocytologic analysis showed that during EHDP treatment viral antigens of the measles type persist in the cytoplasm and nuclei of osteoclasts even when these cells are greatly altered. These findings support the hypothesis of a viral etiology in Paget's disease of bone.

Aged↗
PubMed1984

Effect of a diphosphonate on the osteoinductive activity of rat bone matrix.

Implants of demineralized allogeneic bone were investigated to determine the effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the osteoinductive effect of bone matrix. Implants of matrix prepared from bones of rats treated by EHDP (20 mg/kg/day) produced 40% less ash than implants of normal bone matrix. These results indicate that EHDP not only interferes with mineralization but also has a direct effect on protein metabolism of bone cells.

Animals↗
PubMed1980

[Treatment of Paget's disease of bone with ethane-1 hydroxy-1, 1 diphosphonate at low dosage (author's transl)].

Fifty-one patients with Paget's disease were treated during 6 months with ethane-01 hydroxy-1, 1 diphosphonate (EHDP, etidronate) in doses of 5 mg/kg/day. The drug was most effective in relieving pain, at the same time diminishing the uptake of pagetic lesions on quantitative bone scans and lowering by almost 70% the abnormally high serum alkaline phosphatase levels and 24-hour hydroxyproline urinary levels. Histologically, the resorption surfaces and the number of osteoclasts per mm2 of bone tissue were significantly reduced. On follow-up, the improvement persisted for at least one year after treatment was discontinued. EHDP was well tolerated clinically and biologically, and on histological sections no accumulation of osteoid tissue due to impaired mineralization was seen. EHDP at the 5 mg/kg/day dose appears to be effective in the treatment of Paget's disease.

Adult↗
PubMed1981

[Treatment of Paget's disease of bone: diphosphonates or calcitonin?].

During the past 6 years 16 patients suffering from Paget's disease of bone have been treated and regularly followed up in our department. 10 of these patients have received etidronate (ethane-hydroxy-diphosphonate), 4 others have received synthetic human calcitonin and the last 2 have received both treatments, first successively then simultaneously. Under either therapy satisfactory clinical and biological results have been observed (diminution of pain and decreased levels of serum alkaline phosphatase and hydroxyprolinuria). Etidronate has been more efficient in reducing biological parameters, whereas calcitonin has produced a faster symptomatic response. On the basis of these observations the present principles for treatment of Paget's disease are discussed.

Aged↗
PubMed1981

[Combined treatment of Paget's disease of bone with calcitonin and the diphosphonate EHDP].

To avoid the inhibitory effect of EHDP on bone mineralization, a variety of diphosphonates (Cl2MDP, APD) and a combination of EHDP with calcitonin have been used in the treatment of Paget's disease. In the present study, 13 patients received combined treatment with synthetic human calcitonin (HCT 0.5 mg s.c./day, 5--7 days per week) and EHDP (7.5 mg/kg, day, p.o.) for a mean duration of 6.1 months until disappearance of the symptoms. Results were compared with those obtained in a group of 10 patients treated with HCT alone. The clinical and biochemical effects were similar in both groups, although patients on the combined treatment were treated for a shorter period of time (6.1 vs 11.5 months, p less than 0.01). The desired clinical benefit was obtained within the first few months (4.9 +/- 0.9) in the group on the combined treatment, and within 8.7 +/- 2.4 months (p = 0.05) in the HCT group. Although the incidence of biochemical and scintigraphic relapse was higher than reported in the literature, no clinical recurrence has been observed up to 15 months after interruption of the combined treatment. This positive result casts doubt on the relevance of prolonged treatment of Paget's disease with HCT alone or in combination with EHDP, especially in elderly patients.

Adult↗
PubMedDate not supplied

Failure of osseointegrated dental implants after diphosphonate therapy for osteoporosis: a case report.

Late loss of initially integrated endosseous implants has generally been attributed to implant overload often the result of inappropriate prosthesis design. Implant placement is rarely contraindicated by preexisting systemic diseases, and no instances of medication-induced implant failure have been reported in the literature. This paper reports a case in which a patient lost five endosseous implants that had successfully osseointegrated and had been restored with a lower hybrid prosthesis approximately 6 months after diphosphonate therapy for osteoporosis was started.

Aged↗
PubMed1995

Technetium-99m-methylene diphosphonate scintimammography to image primary breast cancer.

UNLABELLED: Technetium-99m-methylene diphosphonate (MDP) uptake within breast lesions was investigated during routine presurgical bone scintigraphy in a cohort of women at high risk for cancer who were candidates for surgery or excisional biopsy. The aim was twofold: (a) to demonstrate positive 99mTc-MDP uptake in primary breast cancer and (b) to differentiate malignant from benign lesions. METHODS: Anterior and oblique lateral views of the breasts were acquired 0-4 min, 10-20 min and 2 hr after intravenous injection of 740 MBq of 99mTc-MDP in 200 women with elevated suspicion or proven diagnosis of breast cancer (Group 1) and in 80 women with other solid tumor types (Group 2). RESULTS: Physical examination and mammography revealed breast abnormalities in all Group 1 subjects. The mammographic findings were definitely positive for carcinoma in 120 patients, highly suspicious in 27 and indeterminate in 53. Breast cancer was later histologically diagnosed in 172 women (86%) and benign disease found in 28 women (14%). Of these patients, 158 (92%) showed focal uptake of 99mTc-MDP in the images collected 10-20 min after injection. This was found to be the best timing for imaging, with tumor-to-background ratios as high as 4.3 (mean +/- s.d. = 3.8 +/- 0.4). Two hr after injection, only 61 of the 158 (38%) malignant lesions were clearly detectable. CONCLUSION: Technetium-99m-MDP is concentrated by primary breast carcinoma 10-20 min after injection, enabling successful external gamma imaging. Scintimammography with 99mTc-MDP is an accurate test that differentiates malignant from benign breast lesions, particularly in patients with indeterminate mammograms.

Adult↗
PubMed1994

Prevention of corneal allograft rejection in rats treated with subconjunctival injections of liposomes containing dichloromethylene diphosphonate.

PURPOSE: The drug dichloromethylene diphosphonate (CL2MDP) encapsulated in liposomes depletes macrophages but not other immunocompetent cells. The authors investigated whether subconjunctival injection of CL2MDP containing liposomes (CL2MDP-LIP) could prolong survival of corneal allografts in rats. METHODS: Male Fisher rats received orthotopic corneal grafts of Dark Agouti origin. Rats were treated postoperatively with subconjunctival injections of 0.1 ml CL2MDP-LIP at the time of transplantation and on days 2, 4, 6, and 8 after transplantation. Control groups received either liposomes containing phosphate-buffered saline subconjunctivally at the same time points or no additional treatment. Corneal grafts were evaluated every other day and were scored for neovascularization, opacity, and edema. Immunohistologic evaluation was performed 12 and 19 days after surgery. RESULTS: Corneal grafts in both control groups were rejected within 17 days. In the Cl2MDP-LIP treated rats, grafts were not rejected during the maximum follow-up of 100 days. Cellular infiltration in these grafts was clearly reduced. There was also a strong reduction in neovascularization of the cornea. CONCLUSIONS: Rejection of orthotopic allogeneic corneal grafts could be prevented by repeated subconjunctival injection of Cl2MDP-LIP.

Animals↗
PubMed1976

[Melorheostosis in adults. Apropos of 2 cases, 1 of them treated with diphosphonate (EHDP)].

The authors report two cases of melorheostosis discovered in adults because of fairly intense pain and deformation of the affected limb. The radiological appearances were typical. Isotope bone scintigraphy showed strong hyperfixation in the affected bones. A histomorphometric study of a double iliac bone biopsy showed on the one hand, cortical hypertrophy, normal osteonic architecture, and normal lamellar texture in the pathological regions, and, on the other hand, the dynamic character of the healthy bone close the lesions. In one of the patients an original attempt at treatment with diphosphonate (1 200 mg/day of EHDP for 5 months) resulted in a clear improvement in the bone pain. The disease is considered to be a mesodermic dystrophy. It seems to be due to strong hyperactivity of the subperiosteal bone accretion, which, normally, persists only at a weak level in adults.

Adult↗
PubMed1993

Gallium-67 and technetium-99m-methylene diphosphonate skeletal scintigraphy in determining prognosis for children with stage IV neuroblastoma.

Thirty-five children (aged 0-9 yr) who had presented with Stage IV neuroblastoma were studied to see if avidity for 67Ga or 99mTc-methylene diphosphonate (MDP) uptake in both primary and secondary sites at diagnosis conferred any prognostic significance. Twenty-three percent of the patients were disease free and off treatment at the time of study. Crude survival did not differ between groups. Duration of survival and the likelihood of completing treatment were related to the scintigraphic appearance at the time of diagnosis, after adjustment for potential confounding effects, using Cox's proportional hazards regression and multiple logistic regression. After adjustment for confounding influences, neither 67Ga avidity nor uptake of 99mTc-MDP was associated with a significantly worse prognosis, both in terms of adjusted survival and likelihood of completing treatment. Patients with 67Ga-avid scans at diagnosis did not demonstrate significantly worse survival (HR 1.47, 95% CI 0.43-5.11) than those without 67Ga avidity. They were somewhat less likely to complete treatment (OR 0.23, 95% CI 0.03-1.63), but this did not reach statistical significance. Similarly, although patients with 99mTc-MDP positive scans demonstrated somewhat worse survival (HR 2.47, 95% CI 0.45-13.54), this result did not reach statistical significance, nor were they less likely to complete treatment (OR 0.69, 95% CI 0.07-6.67) than those with 99mTc-MDP negative scans. Uptake of 99mTc-MDP into extraosseous sites was also not associated with worse survival (HR 1.45, 95% CI 0.58-3.62) nor with decreased likelihood of completing treatment (OR 0.78, 95% CI 0.12-5.09). Other than indicating disease stage, these results do not support the hypothesis that the scintigraphic appearance at diagnosis confers prognostic information in children with advanced neuroblastoma.

Bone Neoplasms↗
PubMed1996

Scintigraphic evaluation of 99mTc-methylene diphosphonate uptake in the navicular area of horses with lameness isolated to the foot by anesthesia of the palmar digital nerves.

OBJECTIVE: To evaluate distribution and intensity of 99mTc-methylene diphosphonate (99mTc-MDP) uptake in the navicular area in horses with forelimb lameness isolated to the palmar aspect of the foot. DESIGN: Prospective, case-controlled study. ANIMALS: 7 horses with clinical signs of navicular syndrome and 7 control horses. PROCEDURE: Palmar view, soft tissue-phase scintigraphic images of the foot were obtained between 7 and 12 minutes after injection of 120 to 170 mCi of 99mTc-MDP. Lateral and palmar view, bone-phase images were obtained at 30 minutes and 1, 2, and 4 hours after injection. Palmar views were evaluated by determining the ratio of image density in the navicular area to mean image density in the distal phalangeal area. Palmar and lateral view, bone-phase images were also scored on the basis of navicular area intensity (intense = 3, moderate = 2, mild = 1, and no uptake = 0). Density ratios and mean scores were evaluated as a three-way ANOVA. RESULTS: Mean navicular-to-distal phalangeal density ratio for affected horses (1.77) was significantly (P = 0.003) greater than that for control horses (0.97). The mean subjective score for affected horses when evaluating palmar views only (1.85) and when evaluating palmar and lateral view pairs together (1.99) was significantly (P < 0.01) higher than scores for control horses (0.51, 0.62). Images obtained 1 hour after injection were as good at differentiating affected from control horses as images obtained between 2 to 4 hours after injection. CONCLUSION: A substantial number of horses with palmar foot pain have increased scintigraphic uptake within the navicular bone 1 to 4 hours after injection of 99mTc-MDP. Lateral view, bone-phase images are less sensitive than palmar view, bone-phase images in revealing navicular area uptake. CLINICAL RELEVANCE: A combination of lateral and palmar view scintigraphic images obtained between 1 and 4 hours after injection of 99mTc-MDP is a useful diagnostic aid in evaluating navicular bone involvement in horses with forelimb lameness isolated to the palmar aspect of the foot.

Analysis of Variance↗
PubMed1996

Prospective serial technetium diphosphonate and indium-111 white blood cell labeled imaging in primary uncemented total hip arthroplasty.

Although technetium diphosphonate (TcMP) and Indium-111 white blood cell labeled (Ind-WBC) imaging are reported useful in identifying aseptic and septic loosening in cemented hip arthroplasty, their usefulness has not been identified in uncemented porous coated hip arthroplasty. We attempted to define the natural history of TcMP and Ind-WBC imaging in primary P.C.A. uncemented total hip arthroplasty. Twenty-five hips in 21 patients were scanned immediately postoperatively, at 3 months, 6 months, 12 months, 18 months, and 24 months after surgery with both TcMP and Ind-WBC tracers. Clinical and radiographic follow-up were also obtained at each interval. Intensity and distribution of tracer activity were recorded as well as the time when stabilization occurred around the acetabulum, femoral porous surface areas, and femoral stem tip. Acetabular cup and femoral porous surface areas stabilized in the first year on both TcMP and Ind-WBC imaging. Focal femoral hip activity continued at 24 months in 72% of TcMP and 24% of Ind-WBC images. TcMP and Ind-WBC images used to assess uncemented total hip arthroplasty should not be over interpreted. Although persistent intense activity after one year around the acetabulum and porous surface femoral areas should be considered abnormal for both TcMP and Ind-WBC scans, femoral tip activity is present in the majority of patients, with or without thigh pain, at 24 months on TcMP scans. Tip activity can also persist at 24 months on Ind-WBC images and should be interpreted in conjunction with TcMP images.

Acetabulum↗
PubMed1997

Effects of ethane-1-hydroxy-1, 1 diphosphonate on Dunn osteosarcoma cells.

We investigated the effects of ethane-1-hydroxy-1, 1 diphosphonate (EHDP) on Dunn osteosarcoma cells in vivo and in vitro. In in vivo study, an increase of tumor volume was significantly suppressed in the EHDP administered groups compared with the control group. Histologically, Dunn osteosarcoma cells' viability was maintained after EHDP administration. However, fatty degeneration of tumor tissue was suspected in two of eight mice in the 5.0 mg/kg EHDP administered group. In vitro study, EHDP inhibited DNA synthesis and induced morphological changes, such as pycnotic cells. These findings show that the growth of Dunn osteosarcoma cells is inhibited by EHDP.

Alkaline Phosphatase↗
PubMed1997

Etidronate therapy decreases the sensitivity of bone scanning with methylene diphosphonate labelled with technetium-99m.

OBJECTIVE: To define the nature, incidence and consequence of a possible interaction between etidronate (for the treatment of hypercalcemia) and methylene diphosphonate labelled with technetium-99m (99mTc-MDP) (for bone scanning). MATERIALS AND METHODS: The authors reviewed hospital pharmacy records for a period of 2 years and identified 18 patients who had received etidronate. Of this group, 6 patients (4 men and 2 women, ranging in age from 56 to 76 years) had undergone bone scanning with 99mTc-MDP while receiving etidronate. Five of the patients had hypercalcemia associated with metastatic disease, and the sixth had hyperparathyroidism. RESULTS: All bone scans demonstrated poor uptake of tracer by bone accompanied by high soft-tissue background. There was loss of bone definition below the mid-thigh, and in 5 of the 6 patients there was indistinguishable rib uptake. In 1 of the patients, there was absence of uptake in 2 previously defined metastatic lesions. CONCLUSION: Recent oral or intravenous administration of etidronate is a contraindication to bone scintigraphy, as it markedly decreases sensitivity for bone disease. Bone scintigraphy should be timed so that it is performed before etidronate treatment or, if that is not possible, more than 2 to 4 weeks after the therapy has been completed.

Administration, Oral↗
PubMed1976

99MTc-diphosphonate bone imaging and uptake in healing rat extraction sockets.

Clinically positive bone scans of the jaws may result from a variety of benign dental conditions. An experimental system for studying radionuclide imaging and uptake in the jaws of rats was developed. Sequential 99mTc-diphosphonate bone scans and radionuclide uptake determinations were performed on rats after standardized extractions of their mandibular left first molars. Positive bone scans were seen 4-16 days after molar extraction, and increased radionuclide uptake was found in the healing extraction wounds 4-42 days after the extraction. Conventional radiography and histology fail to show unusual bony architecture in extraction sockets at such times. These results correlate with clinical findings in patients and suggest that human beings may have positive bone scans for several months after dental extraction.

Animals↗
PubMed1998

Technetium-99m-methylene diphosphonate scintimammography in male breast cancer.

Breast cancer in men is a rare disease, representing less than 1% of all breast cancers. Recently, scintimammography with 99mTc-methylene diphosphonate (MDP) has been proposed as an effective method in the differential diagnosis of breast masses. A 67-yr-old man with breast cancer that showed avid accumulation of 99mTc-MDP is presented in this article. Infiltrative ductal carcinoma was demonstrated histopathologically.

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