THE DYNAMICS OF SERUM CROSSLAPS AND SCLEROSTIN LEVELS CORRELATES WITH TREATMENT RESPONSE IN MULTIPLE MYELOMA PATIENTS WITH THE PRESENCE OF MYELOMA BONE DISEASE

Background
We performed a prospective study in patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) aimed at the behavior of 13 selected parameters of myeloma bone disease (MBD).

Aims
The aim of our study was to assess the behavior of selected parameters of MBD with respect to therapeutic response.

Methods
Altogether we assessed a cohort of 51 patients: 31 patients with newly diagnosed active MM who responded to treatment reaching at least partial remission (PR) after 4 cycles of chemotherapy, 10 patients with refractory MM (progression or not reaching PR after 4 months), and two control groups – 5 patients with smoldering MM and 5 individuals with MGUS.

The selected parameters of MBD were as follows: serum calcium (Ca), phosphorus (P), procollagen-I N-terminal propeptide (PINP), carboxyterminal telopeptide of type I collagen (ICTP), cross linked C-telopeptide (CTX), osteocalcin (OC), parathormone (PTH), calcitonine (C), 25-hydroxyvitamin D (D2), 1,25 dihydroxyvitamin D (D3), bone fraction of alkaline phosphatase (bALP), sclerostin (Scl) and matrix metallopeptidase 9 (MMP9).

In the whole cohort we performed the analysis of MBD parameters at the time of diagnosis (before start of chemotherapy in active MM) and after 4 months. We assessed the behavior of the parameters with respect to treatment response.

The patients were treated using bortezomib or thalidomide based regimens. All patients with MBD received bisphosphonates and adequte calcium support. In patients undergoing autologous stem cell transplantation the follow-up results were acquired 4 months after the diagnosis but before the transplantion.

For statistical estimation we used Wilcoxon pair test at p ? 0,05, and McNemara test of symetry at p ? 0,05.

Results
We detected significant decrease of CTX (M 0,649 vs. 0,413ug/l; p = 0,014) and sclerostin (M 44,4 vs. 40,6pmol/l; p = 0,030) together with significant increase of parathormone (M 26,0 vs. 60,0pmol/l; p = 0,0005) after 4 months of therapy in patients responding to initial treatment. All the other assessed parameters were without significant change. In patients with refractory MM there was no significant change in any of the assessed parameters. Similarly, there was no significant change in any of the assessed parameters in the control groups, i.e. in patients with smoldering MM, and there was only boderline significant decrease of Ca (M 2,42 vs. 2,28 mmol/l; p =0,042) in MGUS individuals.

Summary
Despite appropriate anti-resorption therapy, there is no change in the parameters of MBD in patients with MM who failed to respond after 4 months of treatment. Patients who respond to therapy have significant decrease of sclerostin and CTX suggesting their auxiliary clinical potential in the assessment of bone turnover in MM patients.

With support of NT14393.

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