melphalan and Osteoporosis

We report a case of 77-year-old woman who presented with lumbago and hypercalcemia. Multiple myeloma (MM) was first diagnosed by serum protein electrophoresis and bone marrow aspiration, but intact parathyroid hormone (intactPTH) was also found to be high in the presence of persistent hypercalcemia with anorexia and nausea. After lowering serum calcium with bisphosphonate administration, parathyroidectomy was performed. Upon histologic examination, the tumor was determined to be parathyroidal chief-cell hyperplasia and the patient was treated with melphalan and prednisolone. The relationship between MM and primary hyperparathyroidism (I degree HPT) remains unknown. Although the co-existence of MM and I degree HPT was reported in 12 reports from various parts of the world, there was only 1 report in Japan. The present case is an example of successful treatment for a complicated disorder, and suggests that patients suffering from bone pain or hypercalcemia need to be examined both endocrinologically and hematologically.

Topics: Aged; Antineoplastic Agents; Female; Humans; Hypercalcemia; Hyperparathyroidism; Hyperplasia; Low Back Pain; Melphalan; Multiple Myeloma; Osteoporosis; Parathyroid Glands; Prednisolone

In 1989, a prospective randomized multicenter study was initiated in order to determine the safety and efficacy of oral clodronate in myeloma patients. The primary objective of this long-term trial is to evaluate whether supportive clodronate is able to prevent or retard the progression of bone disease and reduce the occurrence of characteristic complications: pain, pathologic fractures, and hypercalcemia. We now report first results as an interim analysis, including data obtained from 26 patients (total number of Tübingen patients n = 36) who entered the study at the Medizinische Universitätsklinik Tübingen. Patients were randomized to receive either chemotherapy alone (melphalan 15 mg/m2 i.v. on day 1 and prednisolone 60 mg/m2 orally on days 1-4 every 4 weeks (control group) or in combination with 1600 mg clodronate/day orally as a single dose for a period of at least 1 year. Repeated radiologic examinations in addition to hematologic and biochemical analysis were performed in order to evaluate the skeletal status with respect to lytic bone lesions and osteoporosis and the course of serum M protein and light chain excretion into urine. Clodronate treatment resulted in a significant decrease of serum calcium concentrations and of biochemical indices for bone resorption. No clodronate-related toxicity or hypocalcemia was observed. In patients treated with chemotherapy alone, this effect was less marked and discontinuous. Clodronate-treated patients developed fewer progressive bone lesions (significant for lytic, not for osteoporotic lesions). No hypercalcemic episodes occurred in the clodronate-treated patients, but there were six episodes in the control group. Whereas the number of vertebral fractures was evidently less is clodronate-treated patients, three of those patients suffered from multiple fractures of long bones and ribs. All together, 12 pathologic fractures occurred in five clodronate-treated patients, whereas in the control group 23 pathologic fractures occurred in the same number of patients during the whole observation period. The final analysis of all multicenter included patients should clarify these findings. There was a significant finding that clodronate proved to have an analgesic effect.

Topics: Adult; Aged; Analgesia; Bone Diseases; Bone Resorption; Calcium; Clodronic Acid; Female; Fractures, Bone; Humans; Hypercalcemia; Male; Melphalan; Middle Aged; Multiple Myeloma; Osteoporosis; Prednisolone; Prospective Studies

The bone marrow of the spine, pelvis and proximal femora was examined with MR imaging at diagnosis in 30 cases of multiple myeloma (MM), and during treatment on 69 occasions. The MR pattern was normal, focal or diffuse and correlated to stage. A tumour mass index (TMI) was calculated by estimating the total myeloma mass visualised at MR imaging. The TMI correlated significantly with stage, lytic bone lesions, serum calcium, serum beta-2-microglobulin and survival. No abnormalities were seen at MR investigation in 4 of 6 patients classified as stage II because of osteoporosis only. Therapy efficacy evaluation with MR imaging corresponded to clinical evaluation on 54 of the 69 occasions. MR examination of bone marrow in MM patients can be used for tumour mass assessment, both at diagnosis and during follow-up. Valuable information can be obtained when the tumour mass is difficult to estimate using clinical criteria, e.g. in non-secretory MM or when osteoporosis is the only variable indicating an increase in the tumour mass.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Female; Femur; Humans; Magnetic Resonance Imaging; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Staging; Osteoporosis; Pelvic Bones; Prednisone; Spine

Type I collagen is the main collagen type found in mineralised bone. Specific immunoassays for PICP (carboxyterminal propeptide of type I procollagen) and ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) allow simultaneous assessment of the synthesis and degradation of type I collagen in serum samples, respectively. Our aim was to find out whether these metabolites of type I collagen are useful markers for following bone turnover and evaluating treatment response in multiple myeloma, which is a good model disease of excessive osteolysis. Fifteen consecutive patients were studied before and throughout their treatment. Samples for serum PICP and ICTP were collected before starting each treatment course of melphalan and prednisolon. Response to treatment was evaluated by following the changes in M protein and bone roentgenograms. The disease was progressing in four and regressive in 11 patients, but in four of these a recurrence occurred. In nonresponders the ICTP concentration was permanently elevated despite treatment. In responders both increased or normal levels of ICTP were initially observed, but they returned to or remained in the reference interval during treatment. The ICTP concentration increased upon recurring disease. There was a strong correlation between the extent of bone lesions and ICTP. There was no correlation between ICTP and PICP, the latter mainly remaining within the reference range, a finding that suggests no change in bone formation. ICTP was a significant predictor for survival in this patient group (P less than 0.05). We conclude that ICTP is a specific and sensitive marker for bone resorption. Simultaneous use of serum ICTP and PICP offers an additional and easy means to follow bone turnover and evaluate the response to therapy in multiple myeloma.

Topics: Biomarkers, Tumor; Bone Neoplasms; Calcium; Collagen; Female; Follow-Up Studies; Humans; Immunoglobulins; Male; Melphalan; Middle Aged; Multiple Myeloma; Osteoporosis; Peptide Fragments; Peptides; Prednisolone; Procollagen; Prognosis; Recurrence; Regression Analysis; Time Factors

A 44 year old man with kappa-light plasmacytoma is presented who had been treated for osteoporosis and multiple bone fractures since 12 years. On admittance he had a rapidly progressive myeloma kidney and an extensive extramedullary tumor within the pelvis. Remission was induced using combination chemotherapy according to the VMCP-protocol. It is discussed that the long-lasting osteoporosis of the present case represents an unusually long, monosymptomatic early stage of a multiple myeloma rather than an independent primary disease.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Fractures, Spontaneous; Humans; Male; Melphalan; Multiple Myeloma; Osteoporosis; Prednisone; Vincristine

Plasmocytoma is generally a systemic disorder and has to be differentiated from solitary plasmocytoma of bones and connective tissue. Diagnosis is based on the typical bone marrow findings, the demonstration of monoclonal paraprotein and the radiological skeletal changes. Prognosis is poor, life expectancy limited to about 18 months. Specific therapy with cytotoxic drugs leads in many cases to marked improvement of the general condition, relative freedom of pain and a decreased complication rate.

Topics: Aged; Aging; Bence Jones Protein; Bone Marrow Cells; Cyclophosphamide; Female; Humans; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Osteoporosis; Plasma Cells; Plasmacytoma; Prognosis; Vincristine

A patient with multiple myeloma died of an acute myeloid leukaemia 15 years after onset of the former. At time of diagnosis the 39 year-old-patient had bone marrow infiltration of maximally 32 plasma cells/100 white bone marrow cells, a paraprotein (IgG, light-chain type lambda), osteoporosis of late onset and occasional osteolysis. The long survival time, as well as the acute myeloid leukaemia, are probably due to the effective treatment, first with cyclophosphamide (198 g over four years), later melphalan (3000 mg over eight years).

Topics: Cyclophosphamide; Humans; Immunoglobulin G; Leukemia, Myeloid, Acute; Long-Term Care; Male; Melphalan; Middle Aged; Osteoporosis; Plasmacytoma; Time Factors

The designation "pseudomyeloma'' is used to describe three patients who had a clinical picture that closely resembled multiple myeloma and was characterized by severe osteoporosis and a serum monoclonal paraprotein peak. The diagnosis of myeloma could not be made histologically, initally or after three, four, or ten years of observation. The protein abnormalities and the bone marrow picture remained stable. It is not known if this association has pathophysiologic importance or if it represents a chance phenomenon.

Topics: Blood Protein Disorders; Blood Sedimentation; Bone Marrow Examination; Cyclophosphamide; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunoglobulins; Male; Melphalan; Middle Aged; Multiple Myeloma; Osteoporosis

Topics: Aged; Bone Marrow Cells; Chromatography, Gel; Female; Humans; Immunoelectrophoresis; Lymphoma, Follicular; Male; Melphalan; Middle Aged; Multiple Myeloma; Osteoporosis; Scheuermann Disease; Waldenstrom Macroglobulinemia

Topics: Adult; Aged; Fractures, Bone; Hip; Humans; Lymph Nodes; Male; Maxillary Sinus; Melphalan; Middle Aged; Osteoporosis; Plasmacytoma; Prednisolone; Radiotherapy

Topics: Aged; Bone Marrow; Bone Marrow Cells; Diagnosis, Differential; Fluorescent Antibody Technique; Humans; Immune Sera; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Macroglobulins; Male; Melphalan; Osteoporosis; Plasma Cells; Plasmacytoma; Radiography

Topics: Adrenal Cortex Hormones; Adult; Amyloidosis; Autoimmune Diseases; Bence Jones Protein; Cold Temperature; Cryoglobulins; Humans; Hyperlipidemias; Immunoglobulin M; Male; Melphalan; Mucous Membrane; Multiple Myeloma; Mycosis Fungoides; Osteoporosis; Plasma Cells; Plasmacytoma; Purpura, Hyperglobulinemic; Pyoderma; Skin Manifestations; Skin Ulcer; Tongue; Xanthomatosis

Topics: Anemia; Humans; Hypercalcemia; Melphalan; Multiple Myeloma; Osteoporosis