Person:

Mahindra, Anuj

Osteolytic bone disease is a hallmark of symptomatic multiple myeloma. Bisphosphonates have been the mainstay of treatment to preserve skeletal integrity and prevent skeletal-related events in patients with myeloma-related bone disease. Recently, the MRC Myeloma IX trial demonstrated for the first time improved survival and delayed disease progression with the use of an intravenous amino-bisphosphonate, zoledronic acid, vs. an oral agent, clodronate, with intensive and non-intensive anti-myeloma treatment regimens in patients with newly diagnosed multiple myeloma. These results validate a large body of preclinical, translational and other clinical data suggesting anti-myeloma effects of amino-bisphosphonates. In addition, this trial also provided the first head-to-head evidence for superiority of one bisphosphonate over another (zoledronic acid vs. clodronate) for reducing skeletal morbidity in patients with multiple myeloma, as well as a prospective comparison of toxicities. Despite the use of non-bortezomib containing anti-myeloma treatment regimens in the MRC Myeloma IX trial, these results are encouraging and provide an impetus to continue to evaluate current treatment guidelines for myeloma-associated bone disease.

Bone marrow sarcoidosis is extremely rare. The association between sarcoidosis and lymphoproliferative disorders has been previously speculated, although the diagnosis of sarcoidosis often precedes any hematological derangements. Here, we report for the first time, a case of a 57 year old woman with a previous diagnosis of monoclonal gammopathy of undetermined significance (MGUS) developing hypercalcemia and renal failure with work notable for isolated bone marrow sarcoidosis and not multiple myeloma as expected. The patient was successfully managed with prednisone taper therapy with resolution of her hypercalcemia and repeat bone marrow biopsies demonstrating resolving granulomas. Our case illustrates the diagnostic challenges associated with bone marrow sarcoidosis and suggest that chronic immune stimulation in the bone marrow in the setting of MGUS may be a risk factor for the development of localized sarcoidosis. The long term consequences of steroid therapy targeting sarcoidosis in this patient with underlying MGUS remain unknown. Close followup is planned in light of the increased risk of malignant transformation of MGUS into multiple myeloma in the setting of bone marrow sarcoidosis.