The objective of this study was to investigate the preventive effect of long-acting zoledronic acid on the development of new vertebral fractures in multiple myeloma patients with osteoporosis and/or vertebral fractures.

It is observed that osteolytic lesions in multiple myeloma patients lead to skeletal-related events (SRE), which result in a deterioration in quality of life and a shortened life span. It is estimated that up to 80% of all myeloma patients will experience a skeletal-related event.Although surgical and radiotherapy treatments may be required in specific cases, the most effective approach to avoid recurrence of SREs is to implement preventative measures. The current guidelines for the treatment of myeloma recommend the initiation of bisphosphonate therapy for all patients who meet one of the following criteria: 1. those with osteolytic bone disease, 2. those without bone disease but with symptoms, 3. those with osteoporosis.

It is recommended that zoledronate be administered on a monthly basis for a minimum of 12 months. In terms of the length of treatment, it is indicated that the treatment interval can be extended to once every three months or discontinued in patients who have achieved a VGPR or above in response to myeloma treatment.Zoledronate is available in two different forms as 4 mg and 5 mg. Once-yearly administration of the 5 mg form is indicated for patients with osteoporosis and long-term steroid use. However, there is currently no data supporting the use of the 5 mg form in patients with myeloma.

The Zoledronate 5 mg formulation was administered parenterally, in a 250 cc isotonic solution for a period of 30 minutes, in patients who fulfilled the requisite study criteria. Patients were monitored for any fracture symptoms and side effects related to the administration of zoledronate at each visit to our clinic for myeloma treatment. In cases where a suspected fracture was identified, an MRI assessment was scheduled to be conducted on the relevant area. MRI scan of the spine and pelvis was conducted to assess the effectiveness of the zoledronate treatment at the six-month mark.

The results of the evaluation at six months were available for 16 of the 18 patients. Two patient was excluded from the study due to non-attendance at scheduled control visits and a decision to cease myeloma treatment. All 16 patients underwent a vertebral and pelvic MRI evaluation at the six-month mark. Bone fracture symptoms and biochemical values were assessed at each treatment visit. During the follow-up period, none of the patients reported any symptoms suggestive of new bone fractures. There were no instances of hypocalcaemia, renal dysfunction or albuminuria due to zoledronic acid administration. However, one patient did develop jaw osteonecrosis as a result of dental intervention in the fourth month of zoledronic acid administration.At the six-month MRI examination, none of the patients had developed new fractures.

1. The 5 mg formulation of zoledronate has been proven to prevent the development of new vertebral fractures or the recurrence of fractures in all myeloma patients, regardless of whether they have a fracture or osteoporosis.2. In addition to its efficacy, this application eliminates the shortcomings associated with the aforementioned treatment regimen. With a single administration at the time of diagnosis, compliance is greatly enhanced.3.From a financial perspective, this has a notable impact on the cost of treatment. In Turkey, the lowest monthly price for a 4 mg dose of zoledronate is 884 TL. If the treatment is administered monthly for 12 months, the total cost is 10,608 TL. The cost of a box of denosumab is 4788 TL, with a total treatment cost of 57,456 TL if applied once a month for 12 months. The cost of a box of zoledronate 5 mg is 898 TL, reflecting the annual application frequency.In accordance with the recommendations set forth by the IMWG guideline, the treatment cost of the zoledronate 5 mg formulation is 11 times less expensive than that of the zoledronate 4 mg formulation and 63 times less expensive than that of denosumab, based on a one-year application period. 4. It is recommended that all myeloma patients, with or without osteolytic bone disease, be evaluated for osteoporosis. There is no clear recommendation in this direction in the guidelines. 5. If we add secondary osteoporosis, glucocorticoid use and previous fracture to the FRAX score, we see that all patients are at very high risk of major osteoporotic fracture and hip fracture. This shows that we need to raise awareness in this area.