Effects of Alendronate on Bone Mineral Density in Men with Prostate Cancer Treated with Androgen Deprivation Therapy

Bone mineral density (BMD) is low in men with prostate cancer treated with androgen deprivation therapy (ADT). Intravenous bisphosphonates have been shown to prevent the bone loss, however, the effectiveness of oral bisphosphonates have not been studied in this population. In this retrospective cohort study, we examine the effect of alendronate on BMD in men with prostate cancer receiving ADT. We reviewed the charts of patients receiving ADT referred from the VA Urology Clinic for BMD measurements. Forty seven patients had follow up BMD measurements (17.6 + 8.3 months). Twenty-two men (47%) were also receiving alendronate 70 mg every week. There was a statistically significant difference (p < 0.05) in the percent change of BMD per year at the spine (− 1.29 ± 0.7% vs. + 1.41 ± 0.7%), total hip (− 0.94 ± 0.6% vs. + 0.97 ± 0.5%), femoral neck (− 2.17 ± 0.7% vs. + 0.32 ± 0.6%) and trochanter (− 2.01 ± 0.7% vs. + 0.79 ± 0.8%) in the patients not treated compared to those treated with alendronate. In the four other measured sites at the radius (proximal, mid, ultra distal and total), there were no statistically significant differences (p > 0.05). These findings confirm that bone loss occurs in men receiving ADT at all sites measured. The use of alendronate prevents bone loss at the spine and hip, but does not seem to have the same protective effect at the radius.     

去势治疗对前列腺癌患者骨密度的影响

目的 :探讨去势治疗对前列腺癌患者骨密度 (BMD)的影响。　方法 :4 9例完成BMD测定的前列腺癌患者分为 2组 :非去势组 2 1例 ,在去势治疗前即已完成BMD测定 ;去势组 2 8例 ,均为去势治疗 1年以上者。BMD测定采用双能X线吸收法 (DEXA法 ) ,测定部位为腰椎 (L2～ 4)和股骨颈。为校正年龄、性别和体重因素对BMD的影响 ,与年龄、种族等相配对的Z评分被用于结果评估。　结果 :13例 (6 2 % )非去势组患者和 2 3例 (82 % )去势组患者均存在不同程度的BMD水平下降。在非去势组 ,腰椎 (L2～ 4)Z评分为 - (0 .9± 0 .7)分 ,股骨颈Z评分为 - (0 .6± 0 .5 )分 ;而在去势组 ,腰椎 (L2～ 4)Z评分为 - (1.8± 1.1)分 ,股骨颈Z评分为 - (1.6± 1.0 )分。与非去势组相比 ,去势组患者BMD水平明显偏低 ,差异有显著性 (P <0 .0 1)。　结论 :去势治疗前 ,前列腺癌患者常伴有不同程度的骨量减少和骨质疏松 ,去势治疗与前列腺癌患者BMD水平下降明显相关。在对前列腺癌患者采用去势治疗之前 ,BMD测定是必要的。     

Bisphosphonates in Breast Cancer Patients with Bone Metastases

Morbidity and mortality in breast cancer patients are mainly caused by organ failure as a result of distant metastasis. The main target of metastatic disease is the skeleton (next to lungs and liver). Osseous metastases are diagnosed in 75-80% of all women who die due to breast cancer; and the skeleton is the primary metastatic target organ in more than half of these cases. In Germany, the incidence of breast cancer patients with newly diagnosed bone metastases is approximately 11-12,000 cases. Prevalence might amount to 40,000 cases of women with breast cancer and osseous metastases at a median survival time of 3-4 years. The treatment goal at this stage of the disease comprises improvement of quality of life, and reduction of bone pain and typical complications like fractures and hypercalcemia. By consistent use of bisphosphonates these goals can be accomplished. Bisphosphonates improve bone pain significantly and reduce the number of skeletal-related events in women with bone metastases. Bisphosphonates can be administered intravenously or orally, and are well tolerated. Nevertheless, there are side effects and complications including acute phase reaction, nephrotoxicity, osteonecrosis of the jaw, and gastrointestinal disturbances.     

绝经对妇女骨密度的影响

本文采用双能X线吸收的测量技术测量了16例自然绝经妇女及16例未绝经妇女腰椎骨密度,结果表明,自然绝经妇女骨密度值为1.094±0.1309/cm~2,未绝经妇女组为1.192±0.125g/cm~2,前者低于后者,有统计学意义。而且骨密度与绝经年限成负相关,随绝经年限的延长骨密度逐渐降低,提示,绝经促使骨质丢失,因此绝经妇女及近绝经期妇女应及时采取预防及治疗措施,以减少骨质疏松及骨折的发生。     

Association between Tumor Characteristics and Bone Mineral Density in Postmenopausal Breast Cancer Patients

The aim of this study was to evaluate the association of bone mineral density (BMD) at the time of diagnosis with clinical‐pathologic findings in patients with operable postmenopausal breast cancer. One hundred and fifty‐eight postmenopausal women who had a baseline lumbar and hip BMD measurement were included in the analysis. Patients were divided into two groups based on the median BMD. p ≤ 0.002 was considered to be statistically significant. Hormone replacement therapy (HRT) use longer than 5 years was associated with increased lumbar BMD compared with patients who used HRT less than 5 years (p = 0.002). Patients with higher BMD tended to have low grade disease, no lympho‐vascular invasion, progesterone receptor‐positive tumors, and low Ki‐67 levels (p < 0.05). Higher baseline BMD in postmenopausal patients with breast cancer is associated with favorable prognostic features.     

Prostate Specific Antigen Density is not an Independent Predictor of Response for Prostate Cancer Treated by Conformal Radiotherapy

Although prostate specific antigen (PSA) density appears to be an important discriminator between benign and malignant prostatic disease, conflicting data exist concerning its prognostic value. The present study was undertaken to confirm whether PSA density represents a new prognostic indicator of disease-free survival for prostate cancer treated with conformal radiotherapy. Between April 1989 and December 1992, 186 patients with organ confined prostate cancer were treated with definitive irradiation according to previously published conformal guidelines. The PSA density was defined as the ratio of the pretreatment serum PSA (ng./ml.) to the prostate volume (ml.) as determined from treatment planning computerized tomography. The median PSA density was 0.15 with a range of 0.02 to 2.12. A statistically significant advantage in actuarial freedom from biochemical relapse was noted for patients with pretreatment PSA levels less than 15 ng./ml. when compared to those with higher pretreatment PSA levels (3-year freedom from biochemical relapse 85 percent versus 28 percent, p less than 0.001). Also, patients with PSA density of 0.15 or less had statistically superior freedom from biochemical relapse compared to their counterparts with higher PSA density (3-year freedom from biochemical relapse 88 percent versus 28 percent, p less than 0.001). In a multivariate analysis only the baseline PSA (p less than 0.002) and the Gleason score (p less than 0.002) emerged as significant predictors of prolonged freedom from biochemical relapse. The PSA density had no impact on freedom from biochemical relapse whether it was entered into this multivariate model as a continuous or a dichotomous variable. In our data base baseline PSA levels remain the most powerful independent discriminant of response to conformal irradiation. PSA density is only a surrogate for baseline PSA levels and does not refine the ability to predict prolongation of freedom from biochemical relapse following conformal radiotherapy.     

Osteoprotegerin and Bone Mineral Density in Hemodiafiltration Patients

A newly identified cytokine, osteoprotegerin (OPG) appears to be involved in the regulation of bone remodeling. In vitro studies suggest that OPG, a soluble member of the TNF receptor family of proteins, inhibits osteoclastogenesis by interrupting the intercellular signaling between osteoblastic stromal cells and osteoclast progenitors. As patients with chronic renal failure (CRF) often have renal osteodystrophy (ROD), we investigated the role of osteoprotegerin (OPG) in ROD, and investigated whether there was any relationship between serum OPG, intact parathyroid (PTH) (iPTH), vitamin D, and trabecular bone. Serum OPG combined with iPTH might be a useful tool in the noninvasive diagnosis of ROD, at least in cases in which the range of PTH values compromises reliable diagnosis. Thirty-six patients on maintenance hemodiafiltration (HDF) and a control group of 36 age and sex matched healthy subjects with no known metabolic bone disease were studied. The following assays were made on serum: iPTH, osteocalcin (BGP), bone alkaline phosphatase, 25(OH)-cholecalciferol, calcium, phosphate, OPG, IGF-1, estradiol, and free testosterone. Serum Ca^{+ +}, P, B-ALP, BGP, IGF-1, iPTH, and OPG levels were significantly higher in HDF patients than in controls, while DXA measurements and quantitative ultrasound (QUS) parameters were significantly lower. On grouping patients according to their mean OPG levels, we observed significantly lower serum IGF-1, vitamin D3 concentrations, and lumbar spine and hip bone mineral density in the high OPG groups. No correlation was found between OPG and bone turnover markers, whereas a negative correlation was found between serum OPG and IGF-1 levels (r= ? 0.64, p = 0.032). Serum iPTH concentrations were positively correlated with bone alkaline phosphatase (B-ALP) (r = 0.69, p = 0.038) and BGP (r = 0.92, p < 0.001). The findings made suggest that an increase in OPG levels may be a compensatory response to elevated bone loss. The low bone mineral density (BMD) levels found in the high OPG group might have been due to the significant decrease in serum IGF-1 and vitamin D3 observed. In conclusion, the findings made in the present study demonstrate that increased OPG in hemodiafiltration patients is only partly due to decreased renal clearance. As it may partly reflect a compensatory response to increased bone loss, this parameter might be helpful in the identification of patients with a marked reduction in trabecular BMD.     

Benefits and Limitations of Bone Mineral Density and Bone Turnover Markers to Monitor Patients Treated for Osteoporosis

Medications are approved by regulatory agencies for treating osteoporosis when at least one randomized placebo-controlled clinical trial shows a reduction in vertebral fracture risk and the benefit-risk ratio is determined to be acceptable. Subjects who participate in registration trials are a generally homogeneous group carefully screened with strict entry criteria. Individual patients who are treated for osteoporosis in clinical practice commonly differ from subjects enrolled in these clinical trials according to confounding factors that include age, sex, comorbidities, compliance, and persistence. Because the goal of therapy is reduction of fracture risk, and this cannot be directly assessed in an individual patient, biomarkers are commonly used as surrogate end points for effectiveness. This article reviews the clinical use and abuse of the two biomarkers most commonly used to assess the effectiveness of therapy in clinical practice: bone mineral density testing and measurement of markers of bone turnover.     

Relationships Between Changes in Bone Mineral Density or Bone Turnover Markers and Vertebral Fracture Incidence in Patients Treated with Bazedoxifene

We analyzed the relationships between bone mineral density (BMD) or bone turnover marker (BTM) changes and vertebral fracture incidence in women treated with bazedoxifene using a post hoc analysis from a 3-year randomized, placebo-controlled study evaluating the effect of bazedoxifene (20 or 40?mg) on fracture risk reduction. BMD was assessed at baseline and every 6?months for 3?years. Osteocalcin and C-telopeptide of type I collagen were assessed at baseline and at 3, 12, and 36?months. Vertebral fractures were assessed with a semiquantitative visual assessment. Data were available for 5,244 women, of whom 3,476 were treated with bazedoxifene. Using a logistic regression analysis and the classical Li approach, the proportion of fracture incidence explained by BMD change after 3?years of bazedoxifene treatment was 29?% for the total hip and 44?% for the femoral neck. The proportion of treatment explained by lumbar BMD change could not be quantified accurately because of the significant interaction between treatment and change in BMD. With the same model, the 12-month BTM changes explained up to 29?% of the fracture risk reduction observed with the two forms of bazedoxifene. In women treated with bazedoxifene, changes in femoral neck BMD, hip BMD, or BTMs explained a moderate proportion of the fracture risk reduction observed during the 3?years of follow-up. However, BMD or BTM changes cannot be recommended for individual monitoring of women treated with bazedoxifene.     

Bone Mineral Density in Sixty Adult Patients with Marfan Syndrome

Sixty adult patients (40 women, 20 men) with Marfan syndrome (MFS) according to the Berlin criteria had a full clinical examination and bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry of the hip and nondominant forearm. BMD was expressed as a Z-score and compared with the reference population of the Hologic database. In MFS men, BMD (g/cm²) was compared with the BMD of 45 normal tall Caucasian adults. Osteocalcin was measured by radioimmunoassay. In patients with MFS, BMD was compared between patients with and without previous fractures and according to the phenotypic severity of MFS. The mean age of the patients was 32.9 ± 9.3 years (women 32.5 ± 9.7, men 33.4 ± 8.6), mean height was 180.3 ± 10.3 cm (women 176.3 ± 9.2, men 188.1 ± 7.5) and mean body mass index 20.9 ± 3.6 kg/m² (women 20.8 ± 3.4, men 20.95 ± 3.97). Hyperlaxity score (Beighton criteria) was 6.9 ± 1.1. Six patients (10%) had a previous fracture. Thirty per cent of patients had had at least one previous operation for scoliosis, aortic dilatation or eye problems. BMD values in the 60 patients were as follows: Z-score of the hip, −1.26 ± 0.93, p<10⁻⁹ (neck, −0.93 ± 1.09, p<10⁻⁹; trochanter, −1.31 ± 0.85, p<10⁻⁹; intertrochanter, −1.39 ± 0.99, p<10⁻⁹; Ward’s triangle, −0.93 ± 1.88, p<10⁻⁹); Z-score of the radius: −1.6 ± 1.06, p<10⁻⁹ (1/3 proximal, −1.29 ± 1.03; mid-radius, −1.94 ± 1.04; ultradistal, −0.68 ± 1.1, p<10⁻⁹). The decrease in BMD was similar in men and women at both the hip and the radius. BMD in MFS patients was significantly decreased at cortical compared with trabecular sites (radius 1/3 proximal vs ultradistal, p<0.0001; total femur vs Ward’s triangle, p<0.0005). No difference in BMD was found between MFS patients with or without previous fractures and those with severe or less severe phenotypic expression of MFS. An influence of height and weight in MFS on BMD is suspected. Osteocalcin was not increased in our group of MFS patients. Thus both men and women with MFS have a significant deficit of BMD at the hip and radius. The decrease in BMD is present equally in both sexes and is more pronounced at predominantly cortical sites. In our group of patients we found no increase in fractures and no relation between decreased BMD and phenotypic expression of the syndrome. Received: 30 October 1998 / Accepted: 26 May 1999     

Bone Mineral Density in Patients with Human Immunodeficiency Virus Infection

The Object of this study was to determine whether HIV infection is associated with decreased bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry at total body, lumbar spine, and hip in 45 men with HIV infection and compared with sex, age, and weight-matched controls. Repeat scans were performed after a mean interval of 15 months in 21 patients to determine whether there were detectable losses of BMD. Compared with controls, the HIV patients had marginally lower BMD at the lumbar spine (P= 0.04) but there was no significant difference in total body or hip BMD. None of the patients had reduced BMD to levels associated with a diagnosis of osteoporosis. On longitudinal follow-up, a small decrease in total body BMD (−1.6%; P= 0.02) was observed but there was no significant change in spine and hip BMD. In spite of the many features of HIV infection that might be expected to cause a reduction in BMD such as cytokine activation, decreased physical activity, small bowel disease, hypogonadism, and direct infection of osteogenic cells by HIV, we found only minimal differences in BMD between HIV patients and controls. Furthermore, the HIV patients studied did not appear to show excessive loss in bone mineral over time. Received: 12 November 1996 / Accepted: 5 March 1997     

骨转移瘤放疗后应用安慰护理的临床观察

目的:观察骨转移癌放疗后应用安慰护理的临床效果。方法:52例骨转移癌患者,随机分为安慰护理组和对照组,放疗同时采取不同的护理方式,观察止痛效果、不良反应等临床指标。结果:安慰护理组患者情绪相对平稳,止痛效果明显提高,患者胃肠道反应也相应减轻。结论:放疗后采用安慰护理能提高疗效,有效降低患者痛苦。     

Bone Mineral Density and Bone Turnover in Patients with Knee Osteoarthritis Compared with Generalized Osteoarthritis

The aim of this study was to investigate bone mineral density (BMD) and bone turnover in patients with primary knee osteoarthritis (KOA) and to compare them with generalized OA (GOA) and nonGOA patients. A total of 88 postmenopausal primary KOA patients were studied. OA was graded by using knee radiographs. BMD of the lumber spine, femur, and radius, and biochemical markers of bone turnover, pyridinoline (Pyr), deoxypyridinoline (Dpyr), CTx, and osteocalcin were compared among each grade. BMD was also compared with 88 normal controls who were age and weight-matched. In 88 KOA patients, 56 were divided into 28 GOA and 28 non-GOA groups by grading hand radiographs. BMD and biochemical markers were compared between GOA and non-GOA. KOA patients had higher BMD at several skeletal sites compared with age- and weight-matched normals. A significant difference of BMD between each grade was observed between grades 0–1 and 3 (0.774 ± 0.143 versus 0.940 ± 0.185 g/cm², P < 0.001), grades 2 and 3 (0.781 ± 0.125 versus 0.940 ± 0.185 g/cm², P < 0.01) in the spine, and between grades 0–1 and 3 (0.505 ± 0.100 versus 0.564 ± 0.127 g/cm², P < 0.05) in the trochanter. A significant difference of biochemical bone markers was observed between grades 0–1 and 3 (P < 0.05) and between grades 2 and 3 (P < 0.05) in Pyr and grades 0–1 and 3 (P < 0.05) and between grades 1 and 4 (P < 0.05) in Dpyr, but not in osteocalcin and CTx. GOA patients had higher BMD of the spine (0.902 ± 0.175 versus 0.747 ± 0.138 g/cm², P < 0.01), trochanter (0.535 ± 0.107 versus 0.480 ± 0.107 g/cm², P < 0.05), and one-third of the radius (0.526 ± 0.068 versus 0.472 ± 0.089 g/cm², P < 0.05) and had significantly higher biochemical markers in Pyr and Dpyr than non-GOA patients. It is concluded that KOA patients had higher BMD at several skeletal sites. Biochemical bone markers were influenced by some degree of cartilage damage in OA patients. This tendency was stronger in GOA patients than in non-GOA patients. Received: 12 February 1999 / Accepted: 2 November 1999     

External Validation of a Prognostic Model Predicting Overall Survival in Metastatic Castrate-resistant Prostate Cancer Patients Treated with Abiraterone

A prognostic model was derived from the population of the COU-AA-301 phase 3 trial for metastatic castrate-resistant prostate cancer patients treated with abiraterone after docetaxel, and it stratifies patients into three risk groups based on clinical parameters. We validated this model in an independent cohort of patients treated with abiraterone after docetaxel outside a clinical trial (group A; n = 94) and explored its utility in patients treated with abiraterone in the prechemotherapy setting (group B; n = 64). For group A, median overall survival (mOS) was significantly different across the three prognostic groups (good: n = 39, mOS: 21.8 mo; intermediate: n = 44, mOS: 10.6 mo; poor: n = 7, mOS: 6.8 mo; p < 0.001; area under the curve [AUC]: 0.71). Analysis of group B confirmed the ability of the model to prognosticate for survival in the prechemotherapy setting: (good: n = 44, mOS: 45.6 mo; intermediate or poor: n = 20, mOS: 34.5 mo; p = 0.042; AUC: 0.61). These results serve to validate the prognostic model in an independent population treated with abiraterone after docetaxel and support clinical implementation of the score. Calibration of the model was poorer in patients receiving abiraterone prechemotherapy. Prospective evaluation of this model in clinical trials is needed.