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Robert Marcus

Publications and source records attributed to Robert Marcus.

At least 19 recordsLinked to original sources
PubMed2007

The therapeutic use of rituximab in non-Hodgkin's lymphoma.

The non-Hodgkin's lymphomas (NHLs) comprise a heterogeneous collection of lymphoproliferative malignancies, which are most common in people aged over 55 years. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL, accounting for approximately 30% of all new patients. Follicular lymphoma (FL) is the second most common NHL sub-type, and accounts for a further 22% of cases. While the incidence of most other cancers is decreasing, that of NHL is increasing steadily. During the 1970's and 1980's, worldwide NHL incidence rose by 3-4% per year. This rise has slowed in the 1990's, but an annual increase of 1-2% is still being recorded. Over the last five years, the introduction of monoclonal antibodies, and specifically the anti-CD20 monoclonal antibody, rituximab, has radically changed treatment of B-cell NHL. Rituximab is a genetically engineered chimeric mouse/human monoclonal antibody which binds to the transmembrane antigen, CD20, a non-glycosylated phosphoprotein, located on pre-B and mature B lymphocytes. This antigen is expressed on over 95% of all B cell NHLs, and on normal B cells, but not on haematopoietic stem cells, normal or malignant plasma cells. The Fc domain of rituximab recruits immune effector functions to mediate B cell lysis. Possible mechanisms of cytotoxicity include complement-dependent cytotoxicity (CDC) resulting from C1q binding, and antibody-dependent cellular cytotoxicity (ADCC) mediated by one or more of the Fcgamma receptors on the surface of granulocytes, macrophages and NK cells. It is also possible that the binding of rituximab to the CD20 antigen on the cell surface may directly induce apoptosis. For patients with both follicular and diffuse large B-cell NHL, several large scale prospective randomised trials have demonstrated prolongation of remission when rituximab is incorporated into first line treatment, and, in follicular lymphoma, as a component of salvage therapy. As a result of these studies, current European indications for rituximab include: the treatment of previously untreated patients with stage III-IV follicular lymphoma in combination with cyclophosphamide, vincristine and prednisone (CVP) chemotherapy; as maintenance therapy in patients with relapsed follicular lymphoma responding to induction therapy with chemotherapy or immuno-chemotherapy; the treatment of patients with diffuse large B cell NHL in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. This paper examines the evidence supporting the use of rituximab in these settings, and places its use into the context of standard clinical practice.

Antibodies, Monoclonal↗
PubMed2006

Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma.

PURPOSE: To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study. PATIENTS AND METHODS: Between 1993 and 1997, patients were randomly assigned to treatment with either fludarabine (25 mg/m2 intravenously [IV] daily for 5 days every 4 weeks) or CVP (cyclophosphamide 750 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 1; and prednisone, 40 mg/m2 orally on days 1 through 5 every 4 weeks). Results Overall response (OR) rates were significantly improved in the fludarabine arm versus the CVP arm, both for the intent-to-treat (ITT) population and assessable patients (P < .001). Complete response (CR) rates in the ITT population were also higher after fludarabine treatment. The CR rate was 38.6% for fludarabine compared with 15.0% for CVP. There were no statistically significant differences in time to progression (TTP), time to treatment failure (TTF), and overall survival (OS) between treatment groups. WHO grades 3 and 4 hematologic adverse events were more common in the fludarabine arm. However, concerning the higher incidence of granulocytopenia, this did not translate to more infections in fludarabine-treated patients. CONCLUSION: Newly diagnosed lgNHL patients who received fludarabine achieved higher OR and CR rates compared with CVP-treated patients. No differences in TTP, TTF, and OS were noted. Fludarabine is a highly active single agent in lgNHL. Combination therapies incorporating fludarabine are now being further evaluated as first-line therapy in follicular NHL.

Adult↗
PubMed2006

Novel, high-frequency, low-strain mechanical loading for premenopausal women with low bone mass: early findings.

Universally safe and effective methods of mechanically loading the skeleton to improve strength and prevent fracture have yet to be identified. To be osteogenic, mechanical strains must either be of substantial magnitude or applied at high frequency (>15 Hz). High-magnitude loads place frail bones at risk of fracture. Active loading can rarely be achieved at a frequency faster than 2-3 Hz. A 12-month, uncontrolled, prospective, pilot intervention trial was conducted with five premenopausal Caucasian women with low bone mass. Subjects stood on a vibrating platform (Optimass model 1000 Mechanical Strain Device) and received a 0.2-g stimulus at 30 Hz, 2 x 10 min/day, for 12 months. Bone mineral density (BMD) was measured at the whole body, lumbar spine, proximal femora (PF), and distal radius at baseline and 6 and 12 months by DXA (Hologic QDR-1000/W). Blood and urine were collected at baseline and 3, 6, 9 and 12 months for markers of bone resorption and formation. A mean percent BMD increase of 2.03% +/- 0.33% (P < 0.02) was detected at the non-dominant PF after 12 months. Trends for increases were observed at all other sites with the exception of the dominant PF. No uniform trends were observed in bone resorption and formation markers. One subject, on Fosamax, increased BMD by 6% at the lumbar spine and 4.4% at the distal radius. Preliminary findings provide evidence of a possible positive response of regions of low bone mass to brief daily bouts of in-home, passive, noninvasive, low-strain, high-frequency, mechanical loading.

Adolescent↗
PubMed2006

Initial experience with teriparatide in the United States.

Teriparatide has been commercially available in the United States (US) for over 3 years. This summary spans the early experience with this therapy. As of December 31, 2005, over 235 000 patients had filled a prescription for teriparatide world-wide. Data collected from July to December 2004, from 15,000 retail pharmacies in the US, indicated that the mean age of patients was 67.5 years, and more recent data collected from January through October 2005 indicated that 90% of patients were female. According to market research conducted with prescribing physicians from February through March of 2005, it is estimated that over 80% of patients receiving prescriptions for teriparatide had already experienced one or more prior fractures. Since teriparatide is administered subcutaneously, it is important that patients receive training on the use of the teriparatide injection device (i.e., the pen device). Educational programs are available for those who have been prescribed teriparatide therapy. Patients may also contact a customer care program regarding a variety of topics, including pen device use. Based on patient feedback, design changes have been implemented in the pen device to facilitate optimal use. Updates have also been made to the prescribing information to reflect the post-marketing surveillance experience. Adverse experiences reported to date have been consistent with the current product label and with cumulative teriparatide clinical trial experience. As of December 31, 2005 no reports of pathology-confirmed osteosarcoma have been received for individuals who have been treated with teriparatide, either with the commercially available drug or in clinical trials. We are unaware of any reports of osteosarcoma in association with other preparations of teriparatide, or other peptides of parathyroid hormone, either in the setting of clinical trials or from marketed drug experience.

Aged↗
PubMed2006

Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis.

UNLABELLED: Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo. INTRODUCTION: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. MATERIALS AND METHODS: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. RESULTS: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. CONCLUSIONS: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.

Aged↗
PubMed2005

Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study.

PURPOSE: To describe the response rate and survival of children and adolescents with unresected or metastatic nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) treated with vincristine, ifosfamide, and doxorubicin. PATIENTS AND METHODS: Between September 1996 and June 2000, 39 eligible patients received vincristine (1.5 mg/m(2) weekly for 13 doses), ifosfamide (3 g/m(2) daily for 3 days every 3 weeks for seven cycles), doxorubicin (30 mg/m(2) daily for 2 days for six cycles), and mesna (750 mg/m(2) for four doses after ifosfamide). Granulocyte colony-stimulating factor was administered daily (5 mug/kg) after each cycle of chemotherapy. Radiotherapy was administered from weeks 7 through 12. RESULTS: The median patient age at diagnosis was 11.7 years; the most common primary tumor site was lower extremity (36%); and synovial sarcoma was the predominant histology. More than three fourths of all tumors were 5 cm or greater at their largest diameters. The overall objective combined partial and complete response rate was 41% (95% CI, 25.7% to 56.7%). The estimated 3-year overall survival and progression-free survival rates (+/- standard deviation) for eligible patients were 59% +/- 8.2% and 43.6% +/- 7%, respectively. Patients with clinical group III disease had significantly better 3-year and progression-free survival rates compared with patients who presented with metastatic disease. CONCLUSION: The vincristine, ifosfamide, and doxorubicin regimen was moderately active against pediatric NRSTS. Patients with synovial sarcoma had higher response rates than other patients, and patients with unresected disease had improved outcomes. Patients with metastatic disease continue to fare poorly, and newer approaches are indicated for these patients.

Adolescent↗
PubMed2005

Heritability of plasma sex hormones and hormone binding globulin in adult male twins.

Plasma sex hormone concentrations have been used as biomarkers in epidemiological studies of many conditions including cancer, obesity, bone density, and coronary heart disease. The objective of this analysis was to estimate genetic and nongenetic influences on endogenous sex hormones (testosterone, estradiol, estrone, and SHBG) in a large sample of 532 adult white male twins (134 monozygotic and 132 dizygotic twin pairs) from the National Heart, Lung, and Blood Institute Twin Study. Participants were aged 59-70 yr at the time of plasma collection, and hormone concentrations were determined with RIA. Genetic models were fitted by the method of maximum likelihood. Testosterone and SHBG concentrations have substantial genetic variation, with additive genetic factors accounting for 57 and 68% of the total phenotypic variation, respectively. In contrast, variation in estrone (37% shared environmental and 63% individual specific environmental effects) and estradiol concentrations (25% genetic effect, 44% shared environmental effects, and 31% individual specific environmental effects) were largely influenced by nongenetic factors. Assessment of the relative contribution of genetic and nongenetic influences on hormone concentrations may help in the search for genes underlying variation and covariation in complex traits affected by plasma sex hormone concentrations.

Aged↗
PubMed2005

Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy.

Antiepileptic drugs, particularly cytochrome P450 enzyme inducers, are associated with disorders of bone metabolism. We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine). Subjects completed exercise and nutrition questionnaires and bone mineral density studies. Serum was analyzed for indices of bone metabolism including calcium, 25-hydroxyvitamin D, parathyroid hormone, insulin growth factor I, insulin binding protein III, and bone formation markers, bone-specific alkaline phosphatase, and osteocalcin. Urine was analyzed for cross-linked N-telopeptide of type I collagen, a bone resorption marker. Calcium concentrations were significantly less in subjects receiving carbamazepine, phenytoin, and valproate than in those receiving lamotrigine (p = 0.008). Insulin growth factor-I was significantly reduced in subjects receiving phenytoin compared with those receiving lamotrigine (p = 0.017). Subjects receiving phenytoin had significantly greater levels of bone-specific alkaline phosphatase (p = 0.007). Our results demonstrate that phenytoin is associated with changes in bone metabolism and increased bone turnover. The lower calcium concentrations in subjects taking carbamazepine or valproate compared with those taking other antiepileptic drugs suggest that these antiepileptic drugs may have long-term effects. Subjects receiving lamotrigine had no significant reductions in calcium or increases in markers of bone turnover, suggesting this agent is less likely to have long-term adverse effects on bone.

Adolescent↗
PubMed2005

Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study--a large observational study of the determinants of fracture in older men.

Very little information is available to direct the prevention or management of osteoporosis in men. The Osteoporotic Fractures in Men (MrOS) Study is a prospective cohort study designed to examine the extent to which fracture risk is related to bone mass, bone geometry, lifestyle, anthropometric and neuromuscular measures, and fall propensity, as well as to determine how fractures affect quality of life in men. The study is also designed to understand how osteoporosis is related to prostate disease. At baseline, participants completed questionnaires regarding medical history, medications, physical activity, diet, alcohol intake, and cigarette smoking. Objective measures of anthropometric, neuromuscular, vision, strength, and cognitive variables were obtained. Skeletal assessments included DEXA, calcaneal ultrasound, and vertebral radiographs. Vertebral and proximal femoral QCT was performed on a subset (65%). Serum, urine, and DNA specimens were collected. After the baseline assessments, a questionnaire is mailed to participants every 4 months to ascertain incident falls, fractures, prostate cancer, and deaths. After an average of 4.5 years, participants are scheduled to return for a second comprehensive visit. Men were eligible if > or =65 years. 5995 men enrolled with a mean (+/-SD) age of 73.7 (+/-5.9) years, 11% of which were minorities. Most rated their health as good/excellent. Few were current smokers, although 59% had smoked previously, and 35% reported no alcohol intake, while 47% consumed at least 2 drinks per week. The mean (range) body mass index was 26.9 kg/m2 (17-56). A non-traumatic fracture after age 50 was reported by 17% of the cohort. The MrOS cohort should provide valuable information concerning the determinants of fracture in men and should help set the stage for the development of effective methods to identify those at risk.

Aged↗
PubMed2005

Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation.

Post-transplant lymphoproliferative disorders (PTLD) are a well-recognised and potentially fatal complication after solid organ transplantation. They include a spectrum of disorders ranging from benign hyperplasia to invasive malignant lymphoma. The majority of cases are associated with Epstein Barr virus (EBV)-driven tumour formation in B cells and are a consequence of the detrimental effect of immunosuppressive agents on the immune-control of EBV. This review provides an update on the pathogenesis and clinical features of PTLD after solid organ transplantation and discusses recent progress in management. Reduction in immunosuppressive therapy remains a key component of therapy for EBV-positive PTLD and may lead to remission in early disease. Chemotherapy is used when reduced immunosuppression fails to control early disease and as initial therapy for many cases of late disease. Unfortunately, the mortality for PTLD that fails to respond to a reduction in immunosuppression remains high. Newer treatments include manipulation of the cytokine environment, B lymphocyte depleting antibodies and adoptive T cell immunotherapy using allogeneic or autologous EBV-specific cytotoxic T lymphocytes. Although early results appear promising, well-designed clinical trials are needed to assess the efficacy of these novel approaches. EBV vaccination may in the future prove an effective prophylaxis against EBV-driven PTLD but until then, avoiding excessive immunosuppressive therapy may help minimise the risk of PTLD.

Epstein-Barr Virus Infections↗
PubMed2005

Use of 90Y-ibritumomab tiuxetan in non-Hodgkin's lymphoma.

The increase in the incidence of non-Hodgkin's lymphoma (NHL) that has occurred over recent decades is expected to continue. Therapeutic options for patients with NHL have improved over the past 20 years, but almost all patients with low-grade lymphoma and approximately 50% of patients with high-grade lymphoma eventually die of their disease, regardless of the regimen used. Thus, there is a continuing need for novel therapeutic options. One such strategy is targeted radioimmunotherapy, which is an attractive approach because lymphoma cells are inherently sensitive to radiation. 90 Y-ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, San Diego, CA, and Schering AG, Berlin, Germany) was the first radioimmunotherapy agent to be approved by the US Food and Drug Administration for the treatment of patients with relapsed, low-grade B-cell NHL. 90Y-ibritumomab tiuxetan comprises the murine IgG1 anti-CD20 antibody ibritumomab, covalently linked to the beta-emitter 90 Y by a chelator tiuxetan. A prospective trial comparing 90Y-ibritumomab tiuxetan with single-agent rituximab showed an overall response rate (ORR) to 90Y-ibritumomab tiuxetan of 80% (34% complete response [CR]/unconfirmed CR [CRu]) compared with 56% (20% CR/CRu) with rituximab (P = .002). Of patients achieving a CR/CRu, 32% were still in remission at 3 to 4 years of follow-up. Similar efficacy (83% ORR, 43% CR/CRu) has been reported with 90 Y-ibritumomab tiuxetan in patients with relapsed or refractory low-grade NHL with mild thrombocytopenia (platelet counts 100,000 to 149,000/mm3 ), and in patients with rituximab-refractory NHL (ORR 74% [CR 15%] compared with an ORR 32% to last rituximab treatment). Safety data compiled from patients entered into five studies have confirmed initial observations that the toxicities encountered with 90Y-ibritumomab tiuxetan therapy are mainly hematologic and transient. As part of a consolidated clinical approach to the ongoing development of 90Y-ibritumomab tiuxetan, studies are currently being conducted in the United States and Europe to examine the role of this agent in first-line therapy of indolent NHL, in diffuse large B-cell lymphoma, and in combination with chemotherapy with peripheral blood stem cell support.

Antibodies, Monoclonal↗
PubMed2004

CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma.

The combination of cyclophosphamide, vincristine, and prednisone (CVP) is one of several standard treatment options for advanced follicular lymphoma. This, like similar chemotherapeutic regimens, induces response rates of 60% to 80%, with a median response duration of under 2 years. Rituximab, a chimeric monoclonal antibody against CD20, is active in follicular lymphoma, both as monotherapy and in combination with chemotherapy. Previously untreated patients with stages III to IV follicular lymphoma were randomly assigned to receive either 8 cycles of CVP plus rituximab (R-CVP; n = 162) or CVP (n = 159). Overall and complete response rates were 81% and 41% in the R-CVP arm versus 57% and 10% in the CVP arm, respectively (P < .0001). At a median follow-up of 30 months, patients treated with R-CVP had a very significantly prolonged time to progression (median 32 months versus 15 months for CVP; P < .0001). Median time to treatment failure was 27 months in patients receiving R-CVP and 7 months in the CVP arm (P < .0001). Rituximab did not add significantly to the toxicity of CVP. The addition of rituximab to the CVP regimen significantly improves the clinical outcome in patients with previously untreated advanced follicular lymphoma, without increased toxicity.

Adult↗
PubMed2004

Response to paclitaxel, topotecan, and topotecan-cyclophosphamide in children with untreated disseminated neuroblastoma treated in an upfront phase II investigational window: a pediatric oncology group study.

PURPOSE: Most children older than 1 year of age with metastatic neuroblastoma (NB) die despite intensive chemotherapy and bone marrow transplantation. The Pediatric Oncology Group conducted a study of paclitaxel, topotecan, and topotecan-cyclophosphamide (topo-cyclo) in newly diagnosed children with stage IV NB. PATIENTS AND METHODS: There were 102 patients enrolled between September 1993 and October 1995; two of them were later shown to be ineligible. Of the remaining 100 patients, the first cohort of 33 patients received paclitaxel 350 mg/m(2) intravenously (IV) over 24 hours every 14 to 21 days; the next 33 patients received topotecan 2 mg/m(2)/d for 5 days IV every 21 days; a third cohort of 34 patients were treated with IV cyclophosphamide 250 mg/m(2) followed by topotecan 0.75 mg/m(2) each day for 5 days every 21 days. Patients were re-evaluated after two courses and then treated with intensive induction therapy and bone marrow transplantation. RESULTS: Objective responses (complete response + partial response + mixed response) were documented in 67% of children who received topotecan, 76% after topo-cyclo, and 25% after paclitaxel. Four patients had grade 3 to 4 allergic reactions to paclitaxel; most patients developed grade 3 to 4 marrow suppression after topotecan or topo-cyclo. Neither disease-free survival nor overall survival differed significantly between children who received a phase II agent and those who did not. The 6-year disease-free survival and overall survival rates for all 100 children were 18% +/- 5% and 26% +/- 5%, respectively. CONCLUSION: Topotecan and topo-cyclo are active in children with NB, are well tolerated, and should be evaluated further in combination regimens.

Adolescent↗
PubMed2004

Relationship of endogenous sex hormones to coronary heart disease: a twin study.

We examined the association between endogenous sex hormones (estradiol, estrone, testosterone, and SHBG) and coronary heart disease (CHD) in white male twins. Stored plasma samples were available for 566 participants of the National Heart, Lung, and Blood Institute Twin Study, a longitudinal study of cardiovascular disease in male twins. Twenty-eight of these individuals were lost to follow-up, and outcome data were missing. Of the remaining 538 participants, 78 had CHD at baseline, and 154 subsequently developed CHD over 20 yr of follow-up. We observed no differences in mean unadjusted or age- and body mass index-adjusted log-transformed sex hormone concentrations for participants with and without CHD (all P > 0.08). Quartile and median split analyses revealed no significant association between any of the sex hormones and either prevalent or incident CHD. The discordant monozygotic twins showed no significant case-control group difference in estradiol, estrone, testosterone, and SHBG (all P > 0.3). The positive and negative concordant twin pairs had similar values for each of the sex hormones (all P > 0.3). We observed no relationship between endogenous sex hormone concentrations and prevalent or incident CHD in this sample of male twins.

Adult↗
PubMed2003

Effects of raloxifene, hormone replacement therapy, and placebo on bone turnover in postmenopausal women.

Raloxifene, a nonsteroidal selective estrogen receptor modulator (SERM), increases bone mineral density (BMD), decreases biochemical markers of bone turnover, and prevents incident vertebral fractures in postmenopausal women, while sparing the breast and endometrium from the undesirable stimulation caused by estrogen. How the long-term beneficial effects of raloxifene on bone turnover, as assessed by bone histomorphometry, compare with hormone replacement therapy (HRT) and placebo are not known. We studied 66 healthy postmenopausal women (age 55 to 75 years, mean 63 years) who were randomized to either raloxifene 150 mg/day, HRT (Premarin 0.625 mg/day, and Provera 2.5 mg/day), or placebo for 1 year. All women received 1-1.5 g of calcium/day. Following double tetracycline labeling, transiliac bone biopsies were obtained at baseline and 1 year and analyzed for changes in histologic indexes of bone remodeling on the cancellous surface as well as at the endocortical subdivision of the endosteal envelope, the location of the greatest fraction of postmenopausal bone loss. BMD and biochemical markers of bone turnover were also determined at baseline and 1 year. Four paired biopsies were obtained in the HRT group, six in the raloxifene group, and five in the placebo group. The frequency of remodeling events on cancellous bone and rate of bone formation in both cancellous and endocortical bone increased in the placebo group, while these measurements decreased in both drug treatment groups. Using analysis of mean percentage changes, when compared with the placebo group, these changes were significantly different for both raloxifene and HRT treatment groups (p<0.02). In all subjects, the bone was lamellar with discrete tetracycline labels and there was no evidence of marrow fibrosis or abnormal bone cells. BMD increased from baseline at the lumbar spine (p<0.05 in the HRT group) and in the total body (p<0.05 for both raloxifene and HRT). Compared with that of the raloxifene group, the increase in BMD was greater in the HRT group at the lumbar spine but not in the total body. Serum bone alkaline phosphatase, serum osteocalcin, and urine C-terminal cross-linking telopeptide of type I collagen significantly decreased (p<0.05) in both active treatment groups, changes significantly different from those seen with placebo. Overall, these results support the hypothesis that raloxifene preserves bone mass by reducing the elevated bone turnover found in postmenopausal women receiving placebo, by mechanisms similar to those operative in postmenopausal women receiving HRT.

Aged↗