{'fraction_non_alphanumeric': 0.044620517097581316, 'fraction_numerical': 0.024603836530442035, 'mean_word_length': 4.894348894348894, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Increased bone mineral density in a subset of patients with relapsed multiple myeloma who received the combination of bortezomib, dexamethasone and zoledronic acid.

Bone disease is a major complication of multiple myeloma (MM) [1]. Bortezomib is the first-in-class proteasome inhibitor, with established anti-myeloma activity and beneficial effect on bone metabolism in preclinical studies [2]. In the clinical setting, bortezomib increases bone formation markers, reduces serum levels of osteoblast inhibitor dickkopf-1 [3], increases osteoblast counts in trephine biopsies [4] and inhibits osteoclast function [3, 5]. However, there are no data for bortezomib effect on bone mineral density (BMD) of myeloma patients. To evaluate this effect, we studied 27 consecutive patients (16 males/11 females; median age 69.5 years) with relapsed MM who received the combination of bortezomib plus dexamethasone (VD) and zoledronic acid (ZA): 17 had immunoglobulin G, 6 immunoglobulin A, 3 light-chain and 1 non-secretory MM. Seven patients had International Staging System-1 (ISS-1) MM at diagnosis, while 9 had ISS-2 and 11 ISS-3 MM. The median number of previous lines of therapies was 2 (range 1–5). Bortezomib was given at the standard dose of 1.3 mg/m on days 1, 4, 8 and 11 of a 21-day cycle, while dexamethasone was given at a dose of 20 mg, p.o., the day of bortezomib administration and the following day. All patients received monthly ZA according to their renal function. BMD of the lumbar spine (L1–L4, anteroposterior view) and femoral neck (FN) was measured by dual energy X-ray absorptiometry (DXA) using a Hologic QDR-1000 scanner at baseline (days 27 to day 1 of cycle 1) and then on day 21 of cycle 4 and 1 month after cycle 8. Evidence of myeloma bone disease at the time of relapse was documented by plain radiography. All patients had measurements of urinary Ntelopeptide of collagen type-I (NTX; a sensitive bone resorption marker) and serum bone-specific alkaline phosphatase (bALP) and osteocalcin (OC) (bone formation markers), pre-VD and every month post-VD, using enzyme-linked immunosorbent assay methodology as previously described [3,5]. Differences between preand post-treatment values of the studied parameters were evaluated using the Wilcoxon rank sum test. The study was conducted with ethical committee approval and under the guidelines of the Declaration of Helsinki.