Zoledronic Acid Markedly Improves Bone Mineral Density for Patients with Monoclonal Gammopathy of Undetermined Significance and Bone Loss

Abstract

Purpose: Patients with monoclonal gammopathy of undetermined significance (MGUS) have increased rates of bone resorption, osteopenia, osteoporosis, and risk of fractures. This study was undertaken to determine the efficacy and safety of zoledronic acid for patients with MGUS and enhanced bone loss. Experimental Design: In this phase II open-label study, 54 patients with MGUS and osteopenia or osteoporosis were administered zoledronic acid 4 mg i.v. at 0, 6, and 12 months. The primary efficacy end point was bone mineral density, assessed using a dual-energy X-ray absorptiometry scan in the lumbar (L)-spine done at screening and at 13 months (1 month after the final zoledronic acid infusion). Results: At study end for all patients (N = 54), L-spineT-scores improved by a median of +0.27 (range, -0.38 to +3.91), corresponding to a median increase in bone mineral density of +15.0%(range, -18.0% to +1,140.0%; P < 0.0001). Hip T-scores improved by a median of +0.10 (range, -2.40 to +2.03), corresponding to a median increase of +6.0% (range, -350.0% to +165.0%). During the study, no new fractures, osteonecrosis of the jaw, or significant renal adverse events were reported. Conclusions: Zoledronic acid administered i.v. at a dosage of 4 mg every 6 months for three doses total was well-tolerated and substantially improved bone mineral density for patients with MGUS and bone loss. Zoledronic acid may be effective for the prevention of new fractures in this high-risk population.

Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1α levels in patients with MGUS

“…34 Therefore, avoiding events associated with significant morbidity and mortality-such as fractures-is of paramount importance for patients with MGUS. In 2 studies of short duration, both alendronate 35 and zoledronic acid 36 were shown to increase aBMD in MGUS patients after 18 and 13 months, respectively. Although both bisphosphonates would be expected to decrease fracture risk based on this documented increase in aBMD, this has not yet been demonstrated in randomized trials.…”

Bone disease in monoclonal gammopathy of undetermined significance: results from a screened population-based study

“…Treatment with bisphosphonates has been investigated to some extent in MGUS, and has been shown to increase BMD. 36,37 However, the effect of bisphosphonates on future skeletal-related events and bone structure in MGUS remains uncertain.…”

Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study

“…19 However, 2 studies have evaluated the effect of bisphosphonates in patients with MGUS and have found an improvement in bone mineral density and bone loss. 20,21 Randomized clinical trials are needed to establish the role of bisphosphonates in patients with MGUS.…”