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References 1. Nussbaum SR, Younger J, Vandepol CJ, et al. Single-dose intravenous therapy with pamidronate for the treatment of hypercalcemia of malignancy: comparison of 30-, 60-, and 90-mg dosages. J Med. 1993; 95: 297-304. Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled, clinical trials. J Clin Oncology. 2001; 19: 558-67. Hortobagyi GN, Theriault RL, Porter L, et. al. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer study Group. N Eng J Med. 1996; 335: 1785-91. Hortobagyi GN, Theriault RL, Lipton A, et. al. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer study Group. J Clin Oncol. 1998; 16: 2038-44. Hillner BE, Ingle JN, Chelbowski RT, et.al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003; 21: 4042-57. Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002; 94: 1458-68. Saad F, Gleason DM, Murray R, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004; 96: 879-82. Rosen LS, Gordon D, Tchekmedyian NS, et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with non-small cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind placebocontrolled trial. Cancer. 2004; 100: 2613-21. Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med. 1996; 334: 488-93. Berenson JR, Lichtenstein A, Porter L, et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol. 1998; 16: 593-602 You are in: health & fitness medically speaking joints & bones joints & bones aredia and osteoporosis win: i've got osteoporosis and i'm on the fracture line.
McCann, J. S., and Porter, D. C.: Calcification of the Aorta as an Aid to the Diagnosis of Syphilis. Brit.

Shown azoospermia. He was a body builder and had been abusing steroids. He was advised accordingly regarding the abuse of steroids. A repeat semen analysis after 6 months abstinence from steroids showed a sperm concentration of 1 105 ml with 30% progressive motility and 60% flagellate motility. He was then referred to the regional andrology clinic. On examination testicular volume was normal 20 ml ; , FSH was 1.9 U l, LH 4.6 U l. Testosterone values were not measured due to the small volume of blood available. Five months later the sperm concentration was 6.1 106 ml with 35% progressive motility and 30% flagellate motility. Thirteen months after the cessation of steroid use the sperm concentration was 24.8 106 ml with a progressive motility of 25% and flagellate motility of 15%. After 20 months of abstinence the sperm concentration was 25 106 ml with a 55% progressive motility and 16% flagellate motility. Two months later, 22 months after discontinuing steroids, the couple achieved a pregnancy. Case 4 A 28 year old man was referred with 1 year of primary infertility due to azoospermia. He was a body builder and had been abusing steroids for over 4 years. On examination testicular volume was reduced to 14 ml. On the first investigation azoospermia was confirmed alongside suppressed gonadotrophin levels: FSH 0.7 U l and LH 1.2 U l. Testosterone concentration was 4.2 nmol l. Five months after abstinence, his FSH was 0.9 U l, LH 1.5 U l, testosterone 6.1 nmol l and sperm concentration 51.1 106 ml with 38% progressive motility and 48% flagellate motility. Testicular volume was normal 20 ml ; at that time. A month later the FSH was 0.9 U l, LH 1.5 U l, testosterone 11.2 nmol l, and sperm concentration 106 ml with 31% progressive motility and 50% flagellate motility. The couple achieved a pregnancy by the ninth month following the cessation of steroids. The improvement in sperm concentration of the four cases is summarized in Figure 1. Discussion Steroid abuse by athletes has continued to increase despite the efforts of various sports organizations to curb a practice which.

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Develop tumors in the brain, adrenal gland, and lungs 20 ; , but the earliest symptoms are usually caused by skeletal tumor growth. Hence, the model was therefore considered relevant to study cancer therapy with 223Ra. The results from this study show that animals injected with about 10 kBq of 223Ra had significantly increased symptom-free survival compared with control, indicating that metabolically concentrated -particle emitters irradiating the bone surfaces and calcified tumor sites could slow down progression of skeletal metastases. For comparison, the results of the current study and previous studies exploring various therapeutic modalities in the MT-1 model are presented in Table 1. The data indicate that 223Ra has a significant therapeutic potential for use against metastatic bone disease compared with chemotherapeutic agents, immunotoxins and bisphosphonate labeled with the therapeutic -emitter 131I evaluated in the MT-1 model. Because 223Ra is concentrated in osseous sites including the skeletal surfaces, the antitumor effect of 223Ra may be expected to be independent of the cell characteristics, which may impede the effect of chemotherapeutic agents and immunotoxins. In contrast to immunotoxins, the antitumor effect of 223Ra is not dependent on a high and uniform expression of the antigen on all of the tumor cells and a relatively low cross-reactivity with normal cells. In addition, because 223 Ra is a high LET radiation -emitter, a significant antitumor effect should also be expected on nonproliferating resting ; tumor cells adjacent to the bone surface. The highest activity of 223Ra that was administered in the tumor treatment study corresponded to 0.3 MBq kg b.w. or 30 kBq animal. The therapeutic gain of increasing the dosage beyond the 10 11 kBq animal level was not significant, indicating that a therapeutic plateau was reached with 223Ra. There could be several reasons for this. One reason could be that the complex growth pattern of the tumor model used. Because the uptake of radioactive bone seekers, like radium and strontium, would be in the growth zones of skeletal metastases, i.e., the mineralized interface between the bone and the tumor, and not in the tumor cell itself, the tumor could in some instances be out of reach for the short ranging -particles, e.g., metastases could develop from inside of marrow cavity instead of growing adjacent to the bone surface. The bone metabolism is a complex process involving osteoblasts and osteoclasts, which are cells affecting bone formation and bone resorption. Irradiation could affect the activity of these cells in bone, and if osteoclast-mediated demineralization of bone was the effect, this could cause resorption of radionuclide from the bone. Therefore, additional treatment with the osteoclast inhibitor Aredia was included as a substudy in this work. However, the treatment did not seem to improve therapeutic response at the 30-kBq versus the 10-kBq dose level. In general the therapeutically effective activity of 223Ra seemed to be well tolerated, because no signs of bone marrow toxicity or b.w. loss could be seen in the groups of treated animals. In the experiment with mice, an activity level corresponding to 1 MBq kg was administered without signs of severe bone marrow toxicity or b.w. loss within 3 months after the injection of 223Ra. This indicates that therapeutically relevant doses of 223Ra could be tolerated. 223 Ra decays via a multistep chain releasing four -particles. Another radium isotope with multistep decay chain, i.e., 224Ra, has been used medically in the treatment of noncancerous bone diseases, e.g., ankylosing spondylitis 22, 23 ; . A new study of 224Ra in patients with ankylosing spondylitis was reported recently 24 ; indicating that significant pain relief could be obtained in the majority of patients. Compared with 223Ra the half lives of 224Ra and the nuclides in the decay chain after 224Ra transformation could be less favorable for the purpose of bone targeting. As has been demonstrated in animal.

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We thank research nurses Mrs. E. Lems and Mrs. I. van Slobbe for their assistance. The participating centers were: Free University Hospital Dr. Mieke Houdijk and Prof. Henriette Delamarre ; , Amsterdam; Rijnstate Hospital Dr. Jaap Mulder ; , Arnhem; Catharina Hospital Dr. Johan Waelkens ; , Eindhoven; Beatrix Children's Hospital Dr. Roel Odink ; , Groningen; Medical University Center Leiden Dr. Jet Stokvis ; , Leiden; Canisius Wilhelmina Hospital Dr. Ciska Rongen-Westerlaken ; , Nijmegen; Sophia Children's Hospital Dr. Anita C. S. Hokken-Koelega ; , Rotterdam; Juliana Children's Hospital Dr. Maarten Reeser ; , The Hague; and Wilhelmina Children's Hospital Dr. Maarten Jansen ; , Utrecht, The Netherlands. Received July 8, 2003. Accepted October 31, 2003. Address all correspondence and requests for reprints to: Venje H. Boonstra, M.D., Sophia Children's Hospital Erasmus University Medical Centre, Department of Paediatrics, Division of Endocrinology, Post and arixtra.

Back to top drug contraindications aredia is contraindicated in patients with clinically significant hypersensitivity to bisphosphonates, and those patients undergoing extensive dental procedures Updated Information & Services References including high-resolution figures, can be found at: : content.onlinejacc cgi content full 43 9 1706 This article cites 26 articles, 20 of which you can access for free at: : content.onlinejacc cgi content full 43 9 1706#BIBL This article has been cited by 2 HighWire-hosted articles: : content.onlinejacc cgi content full 43 9 1706#othera rticles Information about reproducing this article in parts figures, tables ; or in its entirety can be found online at: : content.onlinejacc misc permissions.dtl Information about ordering reprints can be found online: : content.onlinejacc misc reprints.dtl and aromasin. And prolonged retention of deciduous teeth. But effects began to appear at six months after the initiation of the therapy and a marked advance in the skeletal maturity and dental development brought about the improvement of the malocclusion with time. These results showed the effectiveness of thyroxine replacement therapy for development of the iaw and eruption of the dentition, as well as importance of thyroxine in normal dentofacial growth.

June 26, 2001--Legislative Changes: PACE Moratorium: Notified Providers that PACE cardholders whose eligibility was terminated in 2001 solely because of a Social Security cost-of-living-adjustment would be reinstated automatically in PACE. An automated process to be established to address PACENET claims for cardholders reinstated into PACE. July 6, 2001--GLEEVECTM: Notified Providers that Novartis Pharmaceutical's anti-cancer drug added to PACE drug file. Approved only for treatment of chronic myelogenous leukemia CML ; and not currently covered by Medicare. Provider should understand that PACE will ensure that drug is approved FDA indication and is prescribed in the approved dosage before authorizing payment. July 13, 2001--Cardholders with July 15, 2001 Ending Eligibility Dates: Notified providers of an extension of eligibility to August 21, 2001. July 20, 2001--Renagel : Notified Providers that effective immediately, only Medical Exception documentation received from prescriber verifying calcium phosphate products of 70 or greater will be considered for the granting of medical exceptions. August 10, 2001--Baycol: Notifies Providers that effective August 9, 2001, PACE no longer reimburses for Baycol because of a voluntary manufacturer withdrawal of the product. August 24, 2001--PACE Moratorium Agreements: Notifies Providers of agreement mailings and of process involved in the provider refunding the cardholder and PACE reimbursing the provider due to the Moratorium. September 21, 2001--Broncholidlator Drugs: Notifies Providers that effective October 1, 2001, the restriction of denying at point-of-sale the reimbursement of these agents has been removed. Medicare remains primary payor. PACE continues to reimburse at 20%, the part not covered by Medicare. September 28, 2001--Miscellaneous Agents, Maximum Dosing Edit: Notifies providers that effective October 8, 2001, PACE will review several new agents. Patients whose prescribing regimen exceeds PACE maximum daily dose will have their prescriber contacted to obtain documentation to support dosing therapy. November 30, 2001--National Drug Code NDC ; Accuracy: Reminds Providers of their responsibilities in accurately reporting NDCs. Discusses prohibited acts. Providers with error rates greater than 50% may be subject to recovery audit and termination. December 14, 2001--Other Prescription Coverage Edit: Specifies proper use of ``Other Coverage Code'' field and identifies NCPDP claim denial responses in the event of improper submission. PACE Provider Bulletins: 2000 February 4, 2000--Medical Exception Authorization. Notified Providers that requests for Medical Exceptions for medications routinely prepared during non-processing hours will not be considered. Requests for Emergency Medical Exceptions for medications dispensed under exceptional circumstances during non-processing hours may be reviewed. February 4, 2000--Other Prescription Coverage. Notified Providers that effective February 14, 2000, PACE will edit claims for PACE cardholders identified by the following insurance carriers: Healthguard; Highmark; Qualmed; Health America; and KHP Central Senior Blue. Claims submitted to PACE for cardholders identified by these companies will deny if the provider submits the claim with an incorrect Other Coverage value of ``0''--``Not Specified'' or ``1''--``No Other Coverage Identified.'' February 11, 2000--Alupent Billing. Notified Providers that to assist providers in maintaining billing consistency, PACE is changing its reimbursement calculation for Alupent 14 gm-10ml, NDC 00597007017 from price per ml to price per gram, effective with dates of service of February 19, 2000 and thereafter. Providers submitting a claim for 1 inhaler of Alupent 14 gm-10 ml, NDC 00597007017 should submit a quantity of 14 in the metric decimal quantity field. February 11, 2000--Medicare Billable Pharmaceuticals Additions. Notified Providers effective February 14, 2000, PACE will reject the following medications at the point-of-service: Synvisc ; Hyalgan ; Polygam ; Imovax ; Leukine ; and Aredia because PACE has been advised that, with the proper diagnosis, physicians may submit these claims to Medicare. March 3, 2000--Duplicate Therapy Edit. Notified Providers that effective March 13, 2000 and thereafter, PACE is implementing a Duplicate Therapy Edit for benzodiazepines and miscellaneous sedative hypnotics. March 24, 2000--Non-Participating Manufacturers. Notified Providers of manufacturers not participating in the PACE Program. March 24, 2000--Propulsid Boxed Warning Revision. Notified Providers that Janssen Pharmaceutica has notified physicians of important changes to its Boxed Warnings, Drug Interactions and Dosage and Administration sections. Highlights of the changes included: 1 ; A 12-lead ECG should be obtained before Propulsid is administered; 2 ; Propulsid should not be initiated if the QTs value exceeds 450 milliseconds; and 3 ; Propulsid is contraindicated in patients with electrolyte disorders hypokalemia, hypocalcemia and hypomagnesemia ; . Serum electrolytes should be assessed in diuretic-treated patients before initiating Propulsid and periodically thereafter. March 24, 2000--Dentist Prescribers. Notified Providers that effective April 3, 2000, and thereafter, claims containing a dentist's license number in the prescriber license number field and submitted for pharmaceuticals other than antibiotics, analgesics, non-steroidals or fluoride preparations will reject with NCPDP Error 88, accompanied by the DUR response ``CH''. March 24, 2000--Duplicate Therapy Edit. Notified Providers effective April 17, 2000 and thereafter, PACE is augmenting its Duplicate Therapy Edit for Benzodiazepines and Miscellaneous Sedative Hypnotics with the inclusion of Ambien and Sonata and artane.

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TRIGG COUNTY AMBULANCE SERVICE PO Box 312 Cadiz, KY 42211 270-522-5555 Ambulance services for transport to medical services. May be covered by some insurances. Site search engines: related searches: bone pain after aredia bone pain after aredia function and arthrotec. The renal safety of 1-hour pamidronate infusion seems to be similar to that of 2-hour infusion in patients treated for multiple myeloma or breast cancer. Overall, we found only 7.7% of patients with clinically significant renal deterioration. This is slightly lower than the 910% reported in randomized, controlled, trials with similar conditions.9, 10, 22 This is the first full report on a lager series of patients treated with 1-hour infusion. Our findings seem to concur with the results reported by other investigators.11 14, 31 33 The majority of these studies involved small numbers of patients, 12, 13, 31, or doses B90 mg.13, 31 33 However, two studies, reported as ASCO abstracts, involved nearly 500 patients. The first study was sponsored by Novartis, the manufac turer of pamidronate Aredia ; . Vilimovskij et al. reported their results of a randomized, controlled, trial on the renal safety of 1-hour infusion of pamidronate 90 mg ; given every 3 to 4 weeks for bone metastases.11 Some 77 patients with multiple myeloma were randomised to 1- or 4-hour infusion, while 128 patients with other unspecified tumor types were randomised to 1- or 2-hour infusion. The median number of doses given was 5 range 111 ; . One-hour infusion was associated with no significant change in SrCr B94 mmol L ; and creatinine clearance B91 mL min ; compared to the longer infusion times. In the second study, Van Poznak et al. reported the results of a single-centred, retrospective, study on the renal safety of 1-hour infusion of pamidronate 90 mg ; in 292 consecutive patients with metastatic breast cancer.14 The median number of treatment cycles given was 17 range: 1 28 ; . patients 5.8% ; , SrCr was above the normal laboratory limit or increased ]44.4 mmol L at the end of pamidronate therapy. One limitation of these two studies is that they did not provide information on renal safety during pamidronate therapy, since the last observed SrCr value was used to assess renal deterioration.11, 14 In addition, the use of an absolute SrCr increase as the only parameter of renal function may be affected by variation on SrCr assay between laboratories and over time. It is interesting that the prevalence of renal deterioration in our dataset was significantly higher when defined by an absolute SrCr increase only 7.7 versus 15% ; . Finally, to date, neither of.
2 3. What is a "wrap-around" and why is it important? The Medicare drug benefit requires all dual eligibles to pay a co-payment of . for every brand name drug and . for every generic drug. The Medicare drug benefit also includes drug formularies see "key terms" above ; . We are very pleased that NJ's newly passed budget includes .6 million which will "wrap-around" the Medicare drug benefit, and cover both the co-payments and the non-formulary medications. This wraparound is for NJ residents. Readers of this article from other states should check with their state officials to learn whether a wrap-around will be available for their state's dual eligibles. ; 4. I heard that the Medicare drug benefit is voluntary. Can a dual eligible decide not to participate in it? It is just a technicality to view this program as voluntary for the dual eligibles. Since the Medicaid drug benefit is ending on December 31, 2005, if a dual eligible completely disenrolls from the Medicare drug benefit, he she won't have any drug coverage at all. Dual eligibles are permitted to switch from one prescription drug plan PDP ; to another by disenrolling from their auto-assigned PDP, and enrolling immediately in a different PDP. However, if they disenroll from one drug plan without simultaneously enrolling in another drug plan, they will not have any coverage for prescription medications. Note: There will be articles in the newspapers and news reports on television and radio that refer to the Medicare drug benefit as "voluntary." However, those reports will be referring to the general Medicare beneficiaries, not to the dual eligibles. 5. In New Jersey, will there be just one Medicare drug plan or many different ones? There will be many different plans. We don't yet know how many, but there could easily be 10 to different Medicare PDPs in New Jersey and possibly even more than that ; . AUTO-ASSIGNMENT AND SWITCHING TO ANOTHER DRUG PLAN 6. How will the dual eligibles enroll in a prescription drug plan PDP ; ? In October 2005, the federal Centers for Medicare and Medicaid Services CMS ; will auto-assign all dual eligibles to a PDP. CMS will send a letter to all dual eligibles or to their representative payee, if the individual has a rep payee ; informing them of the PDP to which they have been assigned. During the middle to end of October, 2005, the dual eligibles and their caregivers and legal guardians should be checking their mail for this important notice from CMS. If the dual eligible or the caregiver or legal guardian ; does not switch to another PDP, then the drug plan named in the October letter from CMS will become the plan that is responsible for the prescription drugs for that individual. However, the dual eligible or the caregiver or legal guardian ; can switch to another PDP beginning on November 15, 2005 ; by calling 1-800-MEDICARE. 7. After receiving the October letter from CMS see the previous question ; , when will the dual eligibles be able to change to a different prescription drug plan PDP ; ? Starting on November 15, 2005, dual eligibles can switch from the drug plan that CMS auto-assigned to another PDP. We have been told that dual eligibles can switch plans up and ascot.

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LIAMS, E. M.: Effects on cardiac muscle of betareceptor antagonists in relation to their activity as local anaesthetics. Brit. J. Pharmacol. 24: 332, 1965. Sonal problems and his controversial history on a number of social issues, Giuliani still shows "vigor and vitality, " according to the polls. Senator McCain, who has appeared to be sort of tired and flat lately, is now coming across as just another "politician" who has charged his positions on a number of important issues.Also, it's quite evident that Romney isn't going to do very well in Alabama. He got no boost from his campaign visit to the state on February 9th. In my opinion, the GOP field is wide open for a candidate who doesn't have the baggage that the current group collectively has. In any event, it's a pretty scary thought when you consider that Giuliani might actually wind up being president. But, it's even scarier that a man like Newt Gingrich is even on the radar screen as a possible leader of our great nation! As for the Democrats, Dr. Johnson's mid-January survey found Senator Clinton with 27% support and Senator Obama with 19%. Speculating about Clinton's improvement in the new poll, it was pointed out that President Clinton's popularity among Democratic voters in Alabama appears to be rubbing off on his wife. As was widely publicized, both of the Clintons and Senator Obama attended Selma's voting rights celebration last month.The most recent poll, which was completed after their appearance in Selma, indicated Senator Clinton benefited more from coming than did Senator Obama. Interestingly, in the new poll, Senator Clinton led among black voters. The only group where Senator Obama finished first was among those ages 18-24. Dr. Johnson, who is a longtime and well-respected Alabama pollster, said the only surprise in the two surveys is what he described as the continuing inability of my good friend John Edwards, a Southerner and former vice-presidential nominee, to catch on with Democrats in Alabama. Frankly, I don't believe that is too significant at this stage. Rather, I believe that the vast amount of free media attention being given to Senators and aspirin. PAP pulmonary artery pressure PVR pulmonary vascular resistance PCWP pulmonary capillary wedge pressure BP systemic blood pressure FEV1 forced expiratory volume in the first second * p 0.05 for before and after values. p 0.05 between the 2 groups. Data from Reference 27 and aredia. Patients We enrolled women with stage IV breast cancer who were receiving cytotoxic chemotherapy and had at least one predominantly lytic, metastatic bone lesion at least 1 cm in diameter. Patients were enrolled at 97 study sites constituting the Protocol 19 Aredia Breast Cancer Study Group ; in the United States, Canada, Australia, and New Zealand from January 1991 through March 1994. All the patients had Eastern Cooperative Oncology Group ECOG ; scores for performance status12 of 0 to the time of enrollment and an estimated life expectancy of at least nine months. In each patient, the presence of a lytic lesion that could be evaluated was confirmed by the central radiologist. Patients were ineligible for the study if they had a skeletal complication a pathologic fracture, the need for radiation to bone or bone surgery, or spinal cord compression due to vertebral collapse ; or a corrected serum calcium concentration corrected for serum albumin concentration ; above 12.0 mg per deciliter 3.0 mmol per liter ; during the two weeks before enrollment, a serum creatinine concentration above 2.5 mg per deciliter 220 mmol per liter ; , ascites or a serum total bilirubin concentration above 2.5 mg per deciliter 43 mmol per liter ; , or a New York Heart Association NYHA ; ranking13 of class III or IV. Patients were also excluded from the study if they were treated with a bisphosphonate except as part of the study ; during the 60 days before enrollment or at any time during the trial or if they had been treated for bone pain with radiation, corticosteroids except as part of the patient's chemotherapeutic regimen ; , calcitonin, or plicamycin during the 2 weeks before enrollment. If a bone lesion had been treated with radiation during the three months before enrollment, it was disqualified from evaluation in this study. During the trial, the chemotherapy regimen but not the study drug ; received by an individual patient could be changed or discontinued at the discretion of the attending oncologist. Study Design Before randomization, eligible patients were stratified according to their ECOG scores for performance status, so that stratum 1 contained patients with scores of 0 or and stratum 2 contained patients with scores of 2 or Within each stratum the patients were randomly assigned in equal numbers ; to receive either 90 mg of pamidronate disodium Aredia, CibaGeigy, Summit, N.J.; administered in 250 ml of 5 percent dextrose in water ; or placebo 250 ml of 5 percent dextrose in water ; , administered 12 times as a two-hour infusion at intervals of four weeks, although the patients were allowed to receive the study drug every three weeks if they were receiving chemotherapy on a three-week schedule. A site-specific, computer-generated randomization list was provided in advance to the study pharmacist at each site, who prepared the medication within 24 hours before and astemizole.

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Greatly depending on what we call the R2-side chain and also whether they're given orally or administered intravenously. They are very poorly and erratically absorbed orally so early trials with oral agents that actually were very active in osteoporosis showed no benefit in the setting of myeloma bone disease. You need a more potent agent, and you need to get more of it in. That is why IV drugs work better than orally [administered drugs]. In the `90s, we published data in which groups of patients received either sugar water or monthly Aredia pamidronate ; , and we showed that patients in the group that received monthly Aredia were much less likely to have a skeletal or bony complication--that is, they were less likely to have a fracture, develop spinal cord compression, or require radiation or surgery to the bone. More recently, zoledronic acid has come on the scene. We began work with this much more potent molecule about 10 years ago. This agent in the laboratory was certainly much better at inhibiting bone loss than any other bisphosphonate including pamidronate, and then about 5 years ago trials were completed comparing this newer agent to pamidronate. The newer agent, Zometa zoledronic acid ; , was given at 4 mg, and Aredia was given at the standard 90 mg to a group of myeloma and breast cancer patients with metastatic bone disease. A number of specific endpoints were looked at in the trial. Although all of them favored Zometa, the statistics did not show significance in favor of Zometa except in 1 of the 4 endpoints, which we call the multiple event analysis. This looked at not only the time-to-first skeletal complication but also the time between subsequent complications and suggests that the newer bisphosphonate is more potent than Aredia to overcome these. Importantly, the new bisphosphonate, Zometa, given at 4 mg can be administered safely over a much shorter period of time, 15 minutes, compared to the 2 hours required for safe administration of pamidronate. This was shown in this comparative trial. Both bisphosphonates, Aredia and the newer one Zometa, are approved when given every 3 to 4 weeks on an ongoing basis because of their ability to reduce bony complications in patients with myeloma bone disease. Let's now put our focus on side effects because this has certainly come up recently. First, I'll mention the flu-like symptoms that occur in perhaps 1 in 5 patients with the first or second dose only. These usually occur about 12 to 48 hours after that first or second infusion. They may last for 6 hours to 24 hours. Importantly, we do not see this with continued dosing except rarely. It's important to recognize that the fever you may have the day after your first or second dose of Aredia or Zometa is actually not occurring from an infection but from the bisphosphonate more than likely.

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