Increased vascularization in myeloma.

Several studies have shown that the number of intratumoral vessels can predict the aggressiveness of a solid cancer, development of metastases and patient survival. Does angiogenesis play an important role in myeloma? The aim of our study was to quantify bone marrow vascularity in various stages of proliferative plasma cell disorders (monoclonal gammopathies of undetermined significance (MGUS), stage I multiple myeloma (MM), stage III MM and Waldenström's macroglobulinemia (WM)) and to compare it with that of patients with osteoporosis. The study included 15 MGUS patients, 15 patients with stage I MM, 15 patients with symptomatic stage III MM, 7 patients with WM, 10 patients with osteoporosis, and 10 patients with reactive bone marrow (RBM), matched for sex and age. After iliac crest biopsy, the various vessels (arterioles, capillaries and sinusoids) were labeled with monoclonal antibodies CD34 and counted, and a histomorphometric study was done. The number of arterioles and arterial capillaries was significantly increased in MGUS and myeloma compared with osteoporosis. The number of arterioles and arterial capillaries increased moderately according to the stage of gravity of myeloma. The number of arterioles is negatively correlated with the trabecular bone volume and positively correlated with the eroded surfaces.

Osteoporosis with lymphoid nodules and hematopoietic marrow hyperplasia.

OBJECTIVE: In 1983 Vigorita reported 3 cases of osteoporosis associated with intramedullary lymphoid nodules. We present 8 patients with osteoporosis and lymphoid nodules (LN) in whom we studied the clinical, biological and histological features and the course of the disease. METHODS: Three men (mean age 52 yrs., range 43-68 yrs.) and 5 women (mean age 60 yrs., 49-66 yrs.), 6 of them with osteoporosis with fracture and 2 with osteoporosis on bone densitometry (T score < -2.5 SD) were enrolled in this study. The following parameters were studied: immunobinding with IG determination, phosphorus and calcium levels, PTH, 25 and 1-25 OH D3, osteocalcin, urinary deoxypyridinoline, histomorphometry, tests for autoanti-bodies, HIV, HTLV, EBV and CMV serology. The results were compared with those of 20 patients with osteoporosis but without LN. Five patients underwent a second BMB a mean of 2 years after the first. RESULTS: Five patients had asthenia, 4 had joint pain and 3 had hyperlymphocytosis. Immunologic and virologic investigations were negative in all cases. Bone marrow was hypercellular (59.9 +/- 5.3 vs 40.1 +/- 13%, p: 0.001). At the second BMB, LN were absent but bone marrow was still hypercellular. In all cases, no cause of demineralization was found and osteoporosis progressed rapidly (an average of 3 vertebral compression fractures in three months, with increased resorption (ES 6.5 +/- 1.6 vs 3 +/- 1.2, p: 0.05) with decreased calcification rate (CR 0.62 +/- 0.07 vs 0.79 +/- 0.1, p: 0.04). CONCLUSION: Some interesting questions are raised by this study. Did an undiscovered viral infection cause the asthenia and joint pain via cytokines or PTHrp in our patients, and can activated lymphocytes perhaps modify bone remodeling?

Histological appearance of the intra-osseous vessels of the femoral head in aseptic osteonecrosis of the hip, with or without antiphospholipid antibodies.

UNLABELLED: It has been suggested that in some patients non-traumatic aseptic osteonecrosis of the hip (AOH) could be the result of the intra-osseous thrombosis. Antiphospholipid antibodies (APL) have been associated with venous and arterial occlusive events and the association between AOH and APL syndrome has been reported. OBJECTIVES: To compare bone vessels of the femoral head in patients operated on for AOH with or without APL. PATIENTS: Twenty patients (mean age 47 yrs) with AOH were included: in eight patients APL (IgG-ELISA) were negative (< 8 GPL units), in nine patients APL were doubtful (8-15 GPL units), and in three patients APL were positive (> 15 GPL units). METHODS: Bone vessels were examined: arteriosclerotic lesions, i.e. fibrosis or thickening of the media and rupture of the internal elastic lamina, thrombosis or vasculitis were sought in the femoral heads after total hip replacement or core decompression. RESULTS: Bone vessel lesions were the same in the three groups.

Effect of ovariectomy on intraosseous vascularization and bone remodelling in rats: action of tiludronate.

In order to study the action of tiludronate on the changes in intraosseous vascularization induced by ovariectomy, and to link these effects to those observed in bone remodelling, 30 female Sprague-Dawley rats (age 40 weeks) were studied. Ten rats were shamoperated and treated by vehicle, 10 rats were ovariectomized and treated by vehicle, and 10 rats were ovariectomized and treated orally with tiludronate, 0.16 mmol/kg/per day, 3 days a week for 16 weeks, from the day following ovariectomy. The rats were killed after 4 months, and a histomorphometric study and quantification of intraosseous vessels carried out on the sixth lumbar vertebra. The area of the intraosseous sinusoidal capillaries increased after ovariectomy, which also induced a moderate increase in resorption surfaces and osteoid surfaces leading to a decrease of 40% in the trabecular bone volume at the lumbar spine level. This bone mineral loss was completely prevented by tiludronate, which normalized the bone turnover. However, tiludronate was without any effect on intraosseous vascularization. These results indicate that the surface area of the intraosseous sinusoidal capillaries was correlated positively with resorption surfaces and negatively with trabecular bone volume and the number of bone trabeculae. In these experimental conditions, an inhibitor of bone resorption can exert its positive effect on bone mass without normalization of vascularization.

Symptomatic osteonecrosis in recipients of nonautologous bone marrow transplants.

A retrospective study of 36 allogeneic bone marrow transplant recipients was conducted to determine the rate of occurrence of and risk factors for avascular osteonecrosis. Eight patients developed osteonecrosis, after a mean time interval of 18 months. Multiple sites were often involved (mean 2.37 per patient). Advanced roentgenologic lesions were present at diagnosis in most instances. The occurrence of osteonecrosis was not significantly correlated with the initial hematologic diagnosis, the preparative regimen, serum lipid abnormalities, presence of acute or chronic graft-versus-host disease, or corticosteroid therapy characteristics. Intraosseous blood vessels exhibited histologic lesions consistent with a role of graft-versus-host-disease vasculitis in the occurrence of osteonecrosis in nonautologous bone marrow transplant recipients.

Study of the intraosseous vessels of the femoral head in patients with fractures of the femoral neck or osteoarthritis of the hip.

Bearing in mind earlier studies which established a link between arteriosclerosis and mineral loss, or fragility of the bones, and also our recent study showing that patients with arterial disorders of the lower limbs also suffered from osteoporosis, we carried out a histological study of the number and appearance of the intraosseous vessels and trabecular bone volume in the femoral heads of patients undergoing surgery for either fracture of the femoral neck or osteoarthritis of the hip. The number of thick-walled vessels, arterioles or arterial capillaries was significantly diminished in the femoral heads of patients with fractures of the femoral neck (p = 0.007). In addition, in the latter patients, arteriosclerotic vascular lesions (rupture of the internal elastic lamina, medial thickening and fibrosis) were more frequent than in patients with osteoarthritis of hip. The possibility that, through chronic ischemia, arteriosclerosis may lead to disturbance of bone remodelling and loss of the mechanical properties of bone has not been contradicted by these findings.