Long Acting Zoledronic Acid Treatment for Vertebral Fracture Prevention in Multipl Myeloma Patients with Osteoporosis

BACKGROUND: Zoledronic acid (zoledronate) is the most commonly used bisphosphonate derivative for the prevention of bone related complications in patients with multiple myeloma. Monthly given and yearly given long acting zoledronate are two different forms of zoledronate. Monthly given zoledronate is the novel agent accepted as the standard treatment for the prevention of multiple myeloma bone related complications. Yearly given long acting zoledronate has no data on the use of multiple myeloma bone disease prevention. AIM:Our primary goal is investigating the vertebral fracture protective effects of a long acting zoledronat agent(Aclasta®) in multiple myeloma patients with associated osteoporosis .We choose vertebrae as the target because bones with the most frequent fractures in multiple myeloma are the vertebrae. As a secondary goal ;we planned to evaluate in preventing fracture development in other bones. METHODS:Patients diagnosed with active multiple myeloma in the Sanlıurfa Mehmet Akif Inan Education and Research Hospital Hematology Clinic at year 2017 were evaluated. Patients fulfilled the inclusion criteria(men and women over the age of 18 and newly diagnosed patients with multiple myeloma,who have lomber vertebra( L1-L4 total or L2-L4) or total femur or femur neck measurements of "(-)1 or lower of any of the T-values" by bone mineral densitometry). Five pa tients were identified who fulfilled these criteria. Four of the patients were female and one patient was male,the age range was between 42 and 76 years.All patients received weekly VCD (bortezomib 1.3 mg /m² cyclophosphamide 500 mg ,dexamethasone 20 mg) intravenously.

During the first administration of chemotherapy , long acting zoledronat (Aclasta®),5 mg was administered with a half-hour intravenous infusion . Simultaneously with the first administration of long acting zolendronat(Aclasta®),600 mg elemental calcium and 400 U vitamin D3 were administered daily to the patients. At the first evaluation time point ,sixth month of treatment beginning ,MRI evaluation of the vertebral column was planned to undergo for all five patients.At the same time patients were questioned for complaints consistent with bone fractures before each chemotherapy session and patients with suspected fracture are planned to be evaluated with MRI.

RESULTS: All patients were in complete remission at the end of the induction treatment.Two of the patients had autologous stem cell transplants.One patient had a tooth extraction before autologous bone marrow transplantation.Any jaw complications did not develop in this patient.None of the five patients developed myeloma-related bone complications ,neither vertebral nor other bones, at the sixth month of therapy.No adverse effects(electrolyte disorders ,albuminuria,etc.) were observed in patients during the administration and follow up period of the drug.

CONCLUSION: It is universaly recommended to apply zoledronate once a month for intravenously at least two years in patients with myeloma. Before every application serum creatinine, serum electrolytes, serum calcium levels and every 3 months albuminuria should be evaluated . Zoledronates have side effects such as fatigue (30%), low blood pressure (11%) and nausea (29%) .Every month we need blood testing to detect electrolyte abnormalities before the therapy and follow up albuminüria as possible side effects of the drug.There is a risk of exposure to side effects every month too.But most important point is ease of application and the cost. Monthly treatment's cost is 1080 USD with it's cheapest generic (U.S market price).When we compare monthly zoledronate with the application of yearly long-acting zoledronate , patients will not have to live all the above-mentioned side effects ,necessity of laboratory evaluation every month, and the cost is only 350 USD with cheapest generic(U.S market price).Long-acting zoledronate is more advantageous considering factors such as cost, ease of administration and frequency of side effects. What is missing here is the large clinical efficacy studies. Our study is first study in the literature and the result are not inconclusive because patient group is very small.But at the same time, we are thinking that long acting zoledronate is a promising agent for preventing bone complications in multiple myeloma patients.So we are planning a phase 3 study to reevaluate our proposal in a larger patient group.