Importance of quantitative histology of bone changes in monoclonal gammopathy

Abstract

Quantitative histology of bone changes, using undecalcified transiliac bone biopsies (UTBB), was performed blindly in 46 individuals with monoclonal gammopathy (MG), including 17 with MG of undetermined significance (MGUS) and 29 with overt multiple myeloma (MM). Three MGUS presented an excess of osteoclastic resorption (OR) in the vicinity of clusters of tumour cells and developed overt B cell malignancies, chronic lymphocytic leukaemia, Waldenström's disease and MM respectively. On the other hand, MGUS with normal OR remained stable (median follow-up = 28 months), with one exception who developed a systemic amyloidosis. In MM, excessive OR was only observed in areas invaded by myeloma cells. OR was frequently normal in active MM lacking myeloma cells in UTBB. Active MM without lesions on radiography had excessive OR. IgA and pure Bence Jones MM appeared more osteoclastic than IgG cases (P less than 0.05). Of major interest was the finding that one third of MM presented histological bone changes similar to osteoporosis, osteosclerosis or osteoblastic metastasis. Two major findings must be emphasized from the current data: UTBB could be of major interest for the early detection of a B cell malignancy; heterogeneity of myeloma bone condition is unexpected. If some changes appear directly related to the tumour (i.e. excessive OR or osteoblastic dysfunction), some others are probably accidentally associated with it (i.e. osteoporosis), both needing treatment other than chemotherapy.

Recruitment of new osteoblasts and osteoclasts is the earliest critical event in the pathogenesis of human multiple myeloma.

“…Until now, the studies have focused on the presence of an excessive bone resorption associated with a low bone formation in patients with advanced MM (4,5,14). Of importance, we have recently demonstrated that this uncoupling process was di- rectly responsible for the lytic bone lesions in myeloma patients (14 (33,34).…”

“…Quantitative histology of bone changes was performed as previously described on undecalcified transiliac bone biopsy specimens (5,14,15). BONE …”

“…Bone involvement is related to an excessive bone resorption encountered in the close vicinity of myeloma cells (3)(4)(5)(6). This increased resorption is due to the local stimulation of osteoclasts by soluble factors released by myeloma cells and environmental cells, such as IL-1 and tumor necrosis factor (TNF) (3,(7)(8)(9)(10)(11)(12)(13).…”

Serum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma

“…The evaluation of the degree of bone involvement in MM and in monoclonal gammopathies of undetermined significance (MGUS, plasma cell dyscrasias which evolve into malignant lymphoplasmocytic diseases in approximately one third of cases (Bladé and Kyle, 1995) could be important for clinical guidance (Bataille et al, 1986), but is limited by the invasiveness of the presently available standard method, the quantitative bone histology. This problem has been partly overcome by the quantification of biochemical markers of bone turnover, such as osteocalcin as a marker of bone formation (Bataille et al, 1990) and the degradation products of type I collagen as indexes of bone resorption (Elomaa et al, 1992;Pecherstorfer et al, 1997).…”

Bone-Resorbing Cells in Multiple Myeloma: Osteoclasts, Myeloma Cell Polykaryons, or Both?

“…This imbalance is particularly evident in patients with advanced MBD and illustrated by histomorphometric studies showing the extreme paucity of newly formed bone near osteolytic lesions [9]. Patients with multiple bone lesions also display a reduction in their serum levels of bone-formation markers, such as alkaline phosphatase, osteocalcin, and procollagen type-I propeptides, coupled with a moderate to severe increase in markers of bone resorption, including ionized calcium levels [10].…”