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PubMed2003

Use of scintigraphy for assessment of fracture healing and early diagnosis of osteomyelitis following fracture repair in rabbits.

OBJECTIVE: To evaluate use of technetium Tc 99m disodium hydroxymethylene diphosphonate (99m-Tc-HDP) for assessing fracture healing and 99m-Tc-HDP and technetium Tc 99m ciprofloxacin (99m-Tc-CIPRO) for early diagnosis of osteomyelitis in rabbits. ANIMALS: 32 skeletally mature New Zealand White rabbits. PROCEDURE: A femoral fracture defect stabilized with bone plates and cortical screws was used. Scintigraphy was performed 4, 8, 12, and 16 weeks after surgery. The 99m-Tc-CIPRO scan was performed 48 hours after the 99m-Tc-HDP scan. The uptake ratio of the experimental limb to the normal limb was calculated by use of multiple regions of interest. Results of radiography performed to determine external callus and lysis grade and percentage defect ossification at 16 weeks were compared with scintigraphy results. RESULTS: Infected fractures had a higher uptake ratio for 99m-Tc-HDP and 99m-Tc-CIPRO than noninfected fractures. Infected fractures could be differentiated from noninfected fractures late in healing by use of 99m-Tc-HDP. Although 99m-Tc-CIPRO was better than 99m-Tc-HDP for identifying infection, there was a high incidence of false positive and negative results with 99m-Tc-CIPRO. There was an association between 99m-Tc-HDP uptake ratio and callus formation and a good correlation between 99m-Tc-HDP uptake ratio and defect ossification after 4 weeks. CONCLUSIONS AND CLINICAL RELEVANCE: 99m-Tc-HDP and 99m-Tc-CIPRO may be useful for diagnosing osteomyelitis late in fracture healing; however, false positive and false negative results occur. Technetium Tc 99m disodium hydroxymethylene diphosphonate may be useful for evaluating fracture healing.

Animals↗
PubMed1982

Etidronate disodium in the treatment of Paget's disease of bone.

Control of Paget's disease of bone has been possible through treatment with agents that decrease bone resorption; calcitonins, diphosphonates, and mithramycin. The pagetic lesion is not, however, cured. Etidronate disodium is one of the diphosphonates. The clinical improvement attained with this drug has to be set against adverse effects, of which pain is probably the most bothersome in practice. Clinical remission can last as long as 2 years after treatment is stopped.

Bone Resorption↗
PubMed1975

Observations on the induction of bone in soft tissues.

Using bone decalcified with 0-6 N hydrochloric acid as an inducing agent, the inductive capacity of different soft tissue sites was investigated. Muscle and fascia regularly permitted the induction of bone, while spleen, liver and kidney suppressed bone induction. Bone formation could be induced in these organs if living autologous fascia was implanted together with the inducing agent; while bone formation was inhibited when living autologous spleen tissue was implanted with the inducing agent to normally favourable sites. The administration of systemic heparin and the diphosphonate ethane-1-hydroxyl, 1-diphosphonic acid (EHDP) suppressed bone induction. It is suggested that for bone induction to occur in soft tissues, three conditions must be present: 1) an inducing agent; 2) an osteogenic precursor cell; and 3) an environment which is permissive to osteogenesis. The presence of osteogenic inhibitors in spleen, liver and kidney is postulated.

Animals↗
PubMed1997

The effect of Lodronat(R) on development of osteoporosis in tail-suspended rats.

It has been recently revealed that deficient loading of the musculoskeletal apparatus gives rise to osteoporosis. It is also a common knowledge, that diphosphonate preparations are used to advantage in clinical practice to prevent and treat osteoporosis of varying etiology. In connection with the above an attempt was made to evaluate potentials of dichlormethylene diphosphonic acid (Lodronat(R), Boehringer Mannheim) as a countermeasure against osteoporosis in tail-suspended rats (micro-g simulation).

Animals↗
PubMed1975

[Treatment of Paget's disease with phosphonates].

A group of 22 patients with Paget's disease of bone was treated with a diphosphonate (sodium etidronate; EHDP), a stable synthetic analogue of inorganic pyrophosphate. This substance was given during 3 months at the dose of 20 mg/kg body weight per day, and proved effective by reducing the raised urinary excretion of total hydroxyproline and by lowering the concentration of serum alcaline phosphatase. It also improved the disease-related osteo-articular pain in 60% of the patients. A rise in serum phosphate under EHDP therapy is due to the increase in renal tubular reabsorption of phosphate. Bone histology showed regression of disease activity and the appearance of lamellar structure in newly formed bone. Because of a transient increase of the amount of uncalcified osteoid, it is advisable to give the diphosphonate in courses not over 3 months or at a reduced daily dose.

Adult↗
PubMed2002

Bone SPECT is more sensitive than MRI in the detection of early osteonecrosis of the femoral head after renal transplantation.

UNLABELLED: We compared the diagnostic sensitivity of (99m)Tc-methylene diphosphonate bone SPECT and MRI in the early detection of femoral head osteonecrosis after renal transplantation. METHODS: The patients were 24 renal allograft recipients who underwent both bone SPECT and MRI within 1 mo of each other because of hip pain but normal findings on plain radiography. SPECT was considered positive for osteonecrosis when a cold defect was detected in the femoral head, and the defect was further classified according to the presence of adjacent increased uptake: type 1 = a cold defect with no adjacent increased uptake; type 2 = a cold defect with adjacent increased uptake. MRI was considered positive for osteonecrosis when a focal region with low signal intensity on T1 images was detected in the femoral head. Final diagnoses were made by surgical pathology or clinical and radiologic follow-up of >1 y. RESULTS: A total of 32 femoral heads, including 24 of 29 painful hips and 8 of 19 asymptomatic contralateral hips, were confirmed as having osteonecrosis. SPECT detected osteonecrosis in all 32 of the femoral heads, resulting in a sensitivity of 100% (32/32), whereas MRI detected osteonecrosis in 21 femoral heads, for a sensitivity of 66% (21/32, P < 0.005). SPECT showed the type 1 pattern in 13 and the type 2 in 19. Ten of the 13 femoral heads with the type 1 pattern were false-negative on MRI, whereas only 1 of 19 with the type 2 pattern was normal on MRI (P < 0.001). There were 6 femoral heads with normal MRI findings and abnormal SPECT findings (type 1 pattern) in 3 patients, for whom hip pain decreased and radiographic findings were normal during follow-up. Follow-up bone SPECT showed a decreasing area of cold defect in 4 femoral heads. CONCLUSION: (99m)Tc-methylene diphosphonate SPECT is more sensitive than MRI for the detection of femoral head osteonecrosis in renal transplant recipients. Bone scintigraphy with SPECT is needed to diagnose osteonecrosis in patients with hip pain despite normal radiography results after renal transplantation. The significance of a transient SPECT abnormality needs to be clarified by further natural history studies.

Adult↗
PubMed2003

Bone uptake studies in rabbits before and after high-dose treatment with 153Sm-EDTMP or 186Re-HEDP.

UNLABELLED: The aim of this animal study was to measure the bone uptake of (99m)Tc-hydroxymethylene diphosphonate (HDP) before and after high-dose treatment with (153)Sm-ethylenediaminetetramethylenephosphonate (EDTMP) or (186)Re-(tin)1,1-hydroxyethylidene diphosphonate (HEDP) to prove or disprove post-therapeutic alterations of bone uptake of radiolabeled bisphosphonates. METHODS: Quantitative bone scanning using 100 MBq (99m)Tc-HDP was performed on 12 rabbits before and 8 wk after radionuclide therapy with 1,000 MBq of either (153)Sm-EDTMP or (186)Re-HEDP. Whole-body images were acquired at 3 min, 3 h, and 24 h after injection, and the activities for the whole body, urinary bladder, and soft tissue were measured by region-of-interest technique. From these data, bone uptake was calculated as initial whole-body activity minus urinary excretion and remainder soft-tissue activity. RESULTS: In animals treated with (153)Sm-EDTMP (n = 6), no differences could be proven for the bone uptake of (99m)Tc-HDP at 24 h after injection before and after therapy (51.1% +/- 5.5% vs. 48.0% +/- 6.1%, P > 0.05). There were also no significant differences for the remainder soft-tissue activities and the urinary excretion rates before and after therapy. Similar results were obtained in rabbits treated with (186)Re-HEDP: Bone uptake (44.8% +/- 6.7% vs. 40.4% +/- 4.9%, P > 0.05) and urinary excretion revealed no significant differences before and after treatment. CONCLUSION: No significant impairment of bone uptake of (99m)Tc-HDP could be observed 8 wk after high-dose radionuclide bone therapy. Because both the biokinetic data obtained for (186)Re-HEDP and (153)Sm-EDTMP and the myelotoxic effects were quite similar in rabbits to those in patients, it seems justifiable to expect the same result (i.e., no significant alteration of bone uptake of radiolabeled bisphosphonates) in patients undergoing a second radionuclide therapy within 2-3 mo after standard treatment with (186)Re-HEDP or (153)Sm-EDTMP.

Animals↗
PubMedDate not supplied

[Effect of chelators of bivalent metal ions on the reaction of myometrium actomoysin superprecipitation].

Kinetic regularities of the reaction of superprecipitation of myometrium actomyosin, as well as the effect of different concentrations of EGTA, EDTA and diphosphonic acids on this process have been studied. Results obtained are of interest from the viewpoint of possible practical use of diphosphonates as factors modifying interaction of the contractile proteins of the uterus smooth muscles under the pathology of contractile response.

Actomyosin↗
PubMed1992

[Prevention of periarticular ossification following endoprosthetic hip replacement using postoperative irradiation].

The development of heterotopic ossification (HO) after total hip replacement or other surgical hip procedures can considerably impair the functional result and quality of life in up to 73% of all patients. Predisposing high risk factors for heterotopic ossification are severe pre-intra- and/or postoperative hip trauma, previous development of ipsi- and/or contralateral heterotopic ossification, hypertrophic osteoarthritis, active rheumatoid spondylarthritis as well as male sex. Over the past two decades a variety of surgical, pharmaceutical and radiotherapeutic prophylactic measurements have been proposed and tested in clinical trials. Since June 1988, we have treated 77 patients or 80 hips respectively with prophylactic irradiation. Individual risk factors included severe coxarthrosis grade IV, ipsi- or contralateral heterotopic ossification and severe hip trauma. As of July 1991 60 patients with a minimum follow-up of six months could be analyzed using clinical and radiological scoring systems. The patients had been prospectively randomized in two different treatment arms: 32 patients were treated with low dose (LD), five times 2 Gy daily fractions to a total dose of 10 Gy, whereas 28 patients were treated with high dose (HD), ten times 2 Gy (eight patients) or five times 3.5 Gy (20 patients). Operative procedures and individual risk factors were equally distributed in both groups. 23 patients (38% received indometacin three times 25 mg for six weeks, 19 patients (32%) diphosphonate EHDP 20 mg/kg body weight and 18 patients (30%) had no additional medication. 56/60 (93%) patients developed no significant heterotopic ossification and/or remained without impairment of their postoperative radiological and clinical hip status according to the applied Brooker and Harris Scores. Only 4/60 (7%) patients demonstrated treatment failures developing postoperative worsening one grade of Brooker score in two patients and two and three grades of Brooker score in the two others. Only 1/49 patients experienced a treatment failure, when radiotherapy had been initiated before and at postoperative day 4 compared to 3/11 patients initiated after postoperative day 4 (p less than 0.001). 3/32 patients (9.4%) in the LD group and 1/28 (3.6%) in the HD group were scored as treatment failures (nonsignificant). Radiotherapy treatment duration and additional medication had no impact on the outcome. In conclusion postoperative radiotherapy has shown high efficacy in prevention of heterotopic ossification as long as the treatment is initiated within the first four days after surgery. With respect to acute toxicity postoperative radiotherapy seems to be without any competition compared to surgical and pharmaceutical approaches including corticoid, diphosphonate and nonsteroid antiphlogistic drugs.

Adult↗
PubMed1975

Technetium-99m-pyrophosphate: studies in vivo and in vitro.

In rats with induced rickets, the uptake of 99mTcO4 and 99mTc-pyrophosphate per gram of bone was increased as compared with weight-matched controls. However, the uptake of radioactive calcium and 32P-pyrophosphate was similar in both rachitic and control animals, suggesting that the 99mTc label conferred specificity and favored the rachitic lesions. Employing the rat tibia in an in vitro system, 99mTcO4 uptake was predominantly in the organic bone matrix; radioactive calcium, 32P-pyrophosphate, or 14C-diphosphonate uptake was mainly in the bone mineral; and 99mTc-pyrophosphate, 99mTc-diphosphonate, and 99mTc-polyphosphate were found in both mineral and organic phases. By removal of both mineral and polysaccharide and by using agents that altered the degree of collagen fibril cross-linking, evidence was obtained suggesting the 99mTcO4 and 99mTc-pyrophosphate are preferentially bound by immature collagen.

Animals↗
PubMed1975

Distributions of several agents useful in imaging myocardial infarcts.

Myocardial cell death due to infarction is accompanied by an influx of calcium ion. The calcium ion seems to localize in crystalline structures that form within mitochondria and resemble hydroxyapatite. Based on this phenomenon 99mTc-stannous pyrophosphate has been successfully used to image myocardial infarcts within 24 hr of infarction and 1 hr following tracer administration both in dogs and patient volunteers. In this report, canine distribution studies of 99m-Tc-pyrophosphate are compared with similar studies with 99mTc-stannous polyphosphate, 99mTc-stannous 1, hydroxy-ethylidene-1, 1-disodium phosphonate diphosphonate), and 18F as sodium fluoride. Pyrophosphate polyphosphate, and diphosphonate are each potentially useful in myocardial infarct imaging but bone uptake of 18F occurs sufficiently early to prevent the use of this radionuclide in infarct scintigraphy.

Animals↗
PubMed2005

Strontium: new drug. Postmenopausal osteoporosis: too many unknowns.

(1) Strontium ranelate is marketed in the European Union for the treatment of postmenopausal osteoporosis. Strontium, a cation closely related to calcium, was already used for this purpose in the 1950s but was abandoned because it caused bone mineralization disorders (mainly due to the high doses used at the time). (2) Strontium has only been compared with placebo: there are no clinical trials versus a diphosphonate. (3) On the basis of bone mineral density, two dose-finding studies suggested that, in women who are also taking calcium and vitamin D, the effective minimal dose of strontium is 1 g/day for primary prevention and 2 g/day for secondary prevention. (4) In secondary prevention, a randomised, double-blind trial (SOTI) involving 1649 postmenopausal women who had already had an osteoporotic fracture and were also taking calcium + vitamin D, showed that 2 g strontium daily reduced the risk of symptomatic vertebral fractures compared with placebo (11.3% versus 17.4%) after three years of treatment. (5) Another randomised, double-blind trial (TROPOS) involved 5091 women with osteoporosis of the femur. After three years of treatment with calcium, vitamin D, and either 2 g/day strontium or placebo, the risk of non vertebral osteoporotic fracture was lower in the strontium arm (10.9% versus 9.1%; relative risk 0.85, 95% confidence interval 0.71-1.01), although the difference was only just significant (p = 0.05). This trial failed to show that strontium reduced the risk of femoral fracture. A retrospective subgroup analysis raised the possibility of a preventive effect on hip fracture in patients aged over 74 years, but again the difference had only borderline significance (relative risk 0.64, confidence interval 0.412-0.997). (6) The SOTI and TROPOS studies were subsequently pooled for analysis. A retrospective subgroup analysis of women aged over 80 suggested some efficacy on non vertebral fractures, but this remains to be confirmed in a comparative trial with relevant outcome measures. (7) The reports of these trials include little information on the adverse effects of strontium. Strontium caused a 50% increase in the risk of venous thromboembolism (including pulmonary embolism). Strontium also increased serum creatine kinase activity in 30% of patients. Strontium can affect mental functions, and this effect needs to be quantified. Neurological and muscular adverse effects were inadequately documented, although disorders of this type were observed in animals. (8) The long-term adverse effects of strontium on bone (osteomalacia, pathological fractures, etc.) are unknown. Data from experimental studies and dialysis patients with renal failure raise the possibility of these adverse effects. (9) In practice, there are too many unknowns surrounding the potential risks of strontium while there is not enough evidence of clinical advantages over diphosphonates.

Aged↗
PubMed1991

Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo.

Rhenium-186 (tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that simultaneously localizes in multiple skeletal metastases in patients with advanced cancer. A single intravenous administration of 30-35 mCi (1110-1295 MBq) is associated with a prompt, significant relief of osseous pain in about 80% of such patients. The efficacy of this new compound was evaluated further by utilizing a double-blind crossover comparison with 99mTc-methylene diphosphonate (MDP) as a radioactive placebo. The new rhenium compound resulted in a significantly (p less than 0.05) greater decrease in pain than did treatment with the radioactive placebo. Rhenium-186(Sn)HEDP appears to be a useful new compound for the palliation of painful skeletal metastases.

Aged↗
PubMedDate not supplied

Bone scintigraphy in acromegaly. Preliminary report on 10 cases.

The present study investigates if bone scintigraphy could be used as a diagnostic and prognostic tool in acromegaly. Bone scintigraphy (99m Tc-diphosphonate) was performed in 10 acromegalic (7 active and 3 inactive acromegaly) vs 12 control patients. Isotope uptake (in counts/cell) was assessed in the area of interest 3-4 hours after diphosphonate administration. Three views were chosen: cranium lateral (I)/frontal (II), and the hands (III). Between the acromegalic and control patients there were significant differences (x = p less than 0.001; xx = p less than 0.05) for the following areas: I-parietal: 66.5 vs 24.82x; I-occipital: 58.4 vs 23x; I-mediosphenoidal temporal: 55.2 vs 21.36x: I-nasal: 55.9 vs 38.73 xx; II-frontal: 46.8 vs 16.64 x; II-nasal: 59.8 vs 40.27 xx; III-left metacarpal: 21.67 vs 15.36 xx; III-right metacarpal: 21.78 vs 16.18 xx. Surprisingly, bone isotope uptake at the mandibular level, both in lateral and frontal view, showed no significant differences between acromegalic and control patients (55.2 vs 45 and 59.8 vs 44.5). Between the active and nonactive acromegalic patients there were no significant differences in any area. Bone scintigraphy, therefore, does not represent a useful index for disease activity. However, the results gave rise to two interesting problems: the acromegalic bone seems to have the same metabolic activity irrespective of the disease status; why is bone isotope uptake the same in acromegalics with pronounced prognathism as in the controls with normal mandible?

Acromegaly↗
PubMed1990

Action of tumoral PTH-related peptide on phosphate and calcium transport.

The recently identified parathyroid hormone-related peptide (PTHrP) exerts several actions on the transport of bone mineral elements. In vitro, the effects of the synthetic amino-terminal fragment of the parathyroid hormone-related protein PTHrP (1-34) on renal cyclic AMP production, Na-dependent Pi transport and Na+/H+ exchange appear to be very similar to PTH (1-34). In vivo, in thyroparathyroidectomized rats, PTHrP reduces the tubular Pi reabsorptive capacity (TmPi/GFR) and thereby lowers the level of plasma Pi. PTHrP (1-34) brings about a dose-dependent elevation in the level of plasma Ca. The hypercalcemic effect of PTHrP (1-34) is due to both an increase in bone Ca resorption, as assessed by an increment in fasting urinary Ca, and an elevation in renal Ca reabsorption. Like PTH, the tumoral peptide does not significantly affect the overall tubular reabsorption of Na. The PTHrP-induced increase in bone Ca resorption is completely inhibitable by diphosphonate therapy. Despite this efficacious antiosteolytic response the fall in calcemia is moderate since the marked effect of PTHrP on the renal transport of Ca is maintained under diphosphonate therapy. These experimental findings are similar to clinical observations previously made with several types of solid tumors.

Biological Transport↗
PubMedDate not supplied

Dialysis-related amyloidosis during peritoneal dialysis.

Patients treated with long-term hemodialysis may develop carpal tunnel syndrome, cystic bone lesions, and/or an arthropathy. This syndrome has been called hemodialysis-related amyloidosis (HRA) and appears to be the result of the accumulation of polymerized Beta-2 microglobulin (B2M). The risk to patients treated with peritoneal dialysis is unknown. Diphosphonate scans have been advocated as a useful noninvasive test for HRA. The authors report a well-documented case of HRA established during hemodialysis and progressing during peritoneal dialysis. In addition, this patient's HRA was not identified by a diphosphonate scan. This is the second well-documented case of HRA associated with peritoneal dialysis.

Aged↗
PubMed1988

[Scintigraphic follow-up of osteosarcoma during neoadjuvant chemotherapy. Results of the cooperative osteosarcoma study of the Society for Pediatric Oncology].

The response of osteosarcomas to preoperative chemotherapy as measured by quantitative 99mTc-diphosphonate scintigraphy was compared with the amount of tumor cell destruction found histologically in the resected specimens. 3-phase bone scintigraphy, with determination of tumor/non-tumor (T/NT) ratios, allowed accurate prediction of tumor response in 28 of 30 tumors (accuracy = 93%) after completion and in 10 of 12 osteosarcomas (83%) at the half-way stage of preoperative chemotherapy, when only those tumors were evaluated which showed convergent changes of T/NT ratios in the perfusion and the mineral phase. At the half-way stage, however, evaluation of chemotherapy effects was complicated in 12 of 23 osteosarcomas by diverging T/NT ratios. In contrast, quantification and mapping of the tumor plasma volume and 99mTc-diphosphonate clearance on parametric images predicted correctly the histological tumor response to chemotherapy in 10 of 11 tumors (91%) after completion and in all 11 cases (100%) at the half-way stage.

Adolescent↗
PubMed1989

Medical treatment of hypercalcemia.

Calcium homeostasis and the symptoms, etiology, and general medical management of hypercalcemia are reviewed. Hypercalcemia, an elevation in total serum calcium concentration, may produce neurologic, gastrointestinal, renal, and cardiovascular disturbances; it may also cause calcification in extraskeletal tissue. Hyperparathyroidism and malignancy cause more than 90% of cases of this potentially fatal disorder. When correction of the underlying cause of hypercalcemia is impossible, calcium-lowering therapy is necessary. Acute management of hypercalcemia often involves rehydration, mobilization of the patient, and furosemide-induced diuresis. These measures may be followed by intravenous administration of etidronate, plicamycin, or calcitonin. Agents used in the long-term management of hypercalcemia include oral phosphates, oral etidronate, intermittent intravenous plicamycin, and, in selected patients, corticosteroids and nonsteroidal anti-inflammatory agents. Investigational calcium-lowering agents include gallium nitrate, ethiofos, dichloromethylene diphosphonate, and aminohydroxyproline diphosphonate. Many agents are available for the treatment of hypercalcemia. Therapy can be individualized by integrating knowledge of the physiologic causes of hypercalcemia, the mechanism of action of calcium-lowering drugs, and the patient's other disease states. Further studies are needed to define the role of investigational calcium-lowering agents.

Adrenal Cortex Hormones↗