Quantitative diagnostic methods in osteoporosis: A review

During the last two decades there have been major advances in the understanding of pathophysiology and in the diagnosis of osteoporosis. There are now, in addition to standard radiographs, a number of different diagnostic modalities available to doctors for the quantitative assessment of bone mass. These methodologies are having an increasingly important role, not only in the clinical diagnosis, but also in the monitoring of patients with osteoporosis. As the population ages there will be an increasing demand for these services, and radiologists need to be aware of the strength and limitations of the different modalities available.     

Low bone mineral density linked to colorectal adenomas: a cross-sectional study of a racially diverse population

Background

Epidemiologic studies suggest that lower bone mineral density (BMD) is associated with an increased risk for colorectal adenoma/cancer, especially in postmenopausal women. The aim of this study is to investigate the association between osteopenia and/or osteoporosis and colorectal adenomas in patients from a New York community hospital.

Methods

We performed a cross-sectional observational study on 200 patients who underwent screening colonoscopies and bone density scan (dual-energy X-ray absorptiometry) at Nassau University Medical Center from November 2009 to March 2011. Among these, 83 patients were identified as osteoporosis (T score of −2.5 or below) and 67 were osteopenia (T score between −1.0 and −2.5). Logistic regression model was performed to assess the association between osteopenia and/or osteoporosis and colorectal adenomas.

Results

Among the patients with osteopenia and osteoporosis, the mean ages were 59.1 years [standard deviation (SD) =8.9] and 61.5 (SD =8.9), respectively. There were 94.0%, 85.1% and 74.7% women, respectively, in normal BMD, osteopenia and osteoporosis groups. The prevalence of colorectal adenomas was 17.9% and 25.3% in the osteopenia and osteoporosis groups, respectively, and 18.0% in the normal BMD group. After adjustment for potential confounders including age, sex, race, body mass index (BMI), tobacco use, alcohol use, history of diabetes, hypertension, or dyslipidemia, osteoporosis was found to be associated with presence of colorectal adenomas more than 2, compared to the normal BMD group. No significant associations were found for the prevalence, size, and location of adenomas.

Conclusions

Our study suggests that osteoporosis is significantly associated with the presence of multiple colorectal adenomas. Prospective studies with a larger sample size are warranted in the future.     

Single infusion of zoledronic acid to prevent androgen deprivation therapy‐induced bone loss in men with hormone‐naive prostate carcinoma

BACKGROUND:

Androgen‐deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone‐naive prostate carcinoma.

METHODS:

Forty men received either a single infusion of zoledronic acid (4 mg intravenously on Day 1) or no infusion during ADT. BMD of the proximal femur and posteroanterior lumbar spine was measured by dual‐energy x‐ray absorptiometry and urinary N‐telopeptide (u‐NTx) at 6 and 12 months.

RESULTS:

At baseline, the overall BMDs demonstrated no significant difference in lumbar spine and hip regions. At 6months, mean (±standard error) BMD of the posteroanterior lumbar spine decreased 4.6% ± 1.0% in control patients and increased 5.1% ± 1.2% in patients receiving zoledronic acid, a significant difference (P = .0002). At 12 months, the change in BMD between the 2 groups was statistically significantly different at the lumbar region (P = .0004), indicating that zoledronate preserved BMD. For u‐NTx, bone turnover was statistically significantly decreased in the zoledronate group compared with controls at 6 months (P < .0001), but returned to pretreatment levels at 12 months in the zoledronate group.

CONCLUSIONS:

Bone loss begins at 6 months with ADT. A single infusion of zoledronic acid in patients receiving ADT reduces bone mineral loss and maintains BMD at least at 12 months during ADT. Further study is needed to determine the best dosing schedule to prevent ADT‐induced bone loss in men with hormone‐naive prostate carcinoma. Cancer 2009. © 2009 American Cancer Society.     

骨密度仪在人体成份测量中的初步应用

目的:探讨骨密度仪在人体成份测量中的的应用价值.方法:应用骨密度仪对肿瘤初诊患者进行人体成份分析,比对皮脂厚度测量、腰围、臀围及体脂率等指标,统计分析其相关性.结果:初步应用骨密度仪测量人体成份结果表明,女性脂肪组织高于男性,肌肉和骨密度则略低.脂肪分布以腰、臀、胸、腿为主,肱三头肌皮脂厚度与骨密度仪上肢脂肪含量测量结果有较好的相关性;腰、腹围和腹、臀部脂肪含量有较好的相关性.结论:皮脂厚度测量和腰、臀围可以较好的反映体内脂肪含量,骨密度仪则能更全面的定量分析人体各部位的骨、肌肉和脂含量,临床可以选择应用评估受检者的营养情况.     

Cancer treatment-induced bone loss: A review

Cancer treatment‐induced bone loss (CTIBL) is the phenomenon of loss of bone mass directly due to the effects of treatment for cancer. There are many causes of CTIBL. This article focuses on CTIBL in the hormone‐dependent cancers (breast and prostate) and reviews the mechanisms, the extent of the problem and the management strategies.     

Segmental trends in cancellous bone structure in the thoracolumbar spine: Histological and radiological comparisons

Segmental variations in vertebral body cancellous bone architecture throughout the thoracolumbar spine were examined using histomorphometry and microradiography, and compared to bone mass measured using dual energy X-ray absorptiometry. In six human vertebral columns (T1 to L5) bone mineral content (BMC) and bone mineral density (BMD) of each vertebral body was determined in the lateral projection. Sagittal plane cancellous bone architecture was assessed from two-dimensional surface stained images and microradiographs of two 1 mm thick sections at each vertebral level. Computer-assisted image analysis was used to measure the total bone area (TBA), mean trabecular width (MTW) and trabecular number (TbN) from the stained images, and the skeletonized network length (SNL) from the radiographic images. Consistent segmental trends were observed for all structural parameters across the six columns examined. Higher TBA and TbN values were observed in the upper thoracic segments and decreased caudally. The MTW was relatively constant in the thoracic vertebrae before increasing in the lumbar spine. Pooled correlations between TBA and the bone density measurements were poor (BMC: r=0.17, BMD: r= 0.25), while the TBA and SNL were only moderately correlated (r= 0.42). In conclusion, histomorphometric and radiological measurements appear to provide different information about cancellous bone structure. Bone structure is poorly correlated to integral measurements of bone mass. The consistent segmental variations in bone architecture appear to reflect a skeletal response to the relative extent of habitually applied loads in different regions of the spine.     

Association between serum uric acid and bone health in general population: a large and multicentre study

Previous studies proposed that serum uric acid (UA), an endogenous antioxidant, could be a protective factor against bone loss. However, recently, a study with a population of US adults did not note the protective effects of serum UA. Therefore, the exact association between serum UA and bone health remains unclear. We performed a retrospective consecutive cohort study in a Chinese population to examine the association between serum UA and bone health. This cross-sectional study included 17,735 individuals who underwent lumbar spine bone mineral density (BMD) measurements as part of a health examination. In covariance analyses (multivariable-adjusted), a high serum UA level was associated with a high BMD, T-score, and Z-score. In binary logistic regression analyses (multivariable-adjusted), a high serum UA level was associated with low odds ratios (ORs) for at least osteopenia and osteoporosis in male (age ≥50 years) (OR = 0.72–0.60 and OR = 0.49–0.39, respectively) and postmenopausal female participants (OR = 0.61–0.51 and OR = 0.66–0.49, respectively). In conclusion, serum UA is associated with BMD, the T-score, and the Z-score, and has a strong protective effect against at least osteopenia and osteoporosis.     

The effect of clodronate and antioestrogens on bone loss associated with oestrogen withdrawal in postmenopausal women with breast cancer

In this study we report bone mineral density (BMD) changes during clodronate and antioestrogen treatment in women with breast cancer having discontinued hormone replacement therapy (HRT) at the time of operation compared to women who had not used HRT immediately before the operation. 61 postmenopausal women with operable breast cancer were treated with the adjuvant antioestrogen tamoxifen 20 mg or toremifene 60 mg daily for 3 years. All patients were randomized to clodronate (1.6 g daily orally) or control groups for 3 years. 23 patients had recently (recent users) and 38 never or not for at least 1 year before operation used HRT (non-users). BMD of lumbar spine and femoral neck were measured before antiresorptive therapy (antioestrogens and clodronate) and at 1, 2, 3 and 5 years thereafter. All patients were disease-free at the time of BMD measurements. Patients who had recently used HRT had more significant bone loss as compared to HRT non-users at 3 years in lumbar spine - 3.0% vs. + 1.2% (P< 0.001), but not in femoral neck - 0.4% vs. + 1.7% (P = 0.27). Adding 3-year clodronate treatment to antioestrogen therapy improved BMD marginally at 3 years: lumbar spine + 1.0% vs. -1.7% (P = 0.01) and femoral neck + 2.4% vs. -0.4% (P = 0.12). This was also seen at 5 years of follow-up, 2 years after termination of the antiresorptive therapy: HRT recent users vs. HRT non-users in lumbar spine -6.5% vs. +0.5% (P< 0.0001) and in femoral neck -4.8% vs. -1.5% (P = 0.38); and clodronate vs. controls in lumbar spine -1.0% vs. -3.2% (P = 0.06) and in femoral neck -0.1% vs. -5.2% (P = 0.001, respectively). The type of endocrine therapy (tamoxifen and toremifene) had no significant influence on BMD changes. We conclude from this study that postmenopausal women who have recently discontinued HRT experience more rapid bone loss than HRT non-users. Neither 3-year antioestrogen therapy alone nor antioestrogen together with clodronate could totally prevent the bone loss related to HRT withdrawal in lumbar spine, even though clodronate seemed to retard it.     

鲑鱼降钙素治疗老年骨质疏松症的疗效观察

目的　观察鲑鱼降钙素对老年骨质疏松症的治疗效果。方法　将经定量CT(QCT)测定确 诊为骨质疏松且有临床症状的老年患者105例分成两组,鲑鱼降钙素组48例,予鲑鱼降钙素肌肉注射,每 天1次50IU,连用7d后,改为50IU隔天1次,连用14d后,改为50IU每周2次,连用4周为一个疗程,间 隔2个月后再重复,共1年,同时加服钙尔奇D(含元素钙600mg,维生素D125IU)每天1片;钙剂组57 例,单纯口服钙尔奇D每天1片,疗程1年,两组治疗前后均测定2～4腰椎(L2～4)骨密度(BMD),治疗前 后记录临床症状。结果　鲑鱼降钙素组较钙剂组骨痛症状缓解(89.6%和42.1%)效果明显(P<0.01), 鲑鱼降钙素组腰椎BMD治疗后(0.85±0.09)mg/cm3,较治疗前(0.81±0.05)mg/cm3有所升高(P< 0.05);钙剂组BMD无明显改变。结论　鲑鱼降钙素与钙剂联合应用对治疗老年骨质疏松症有缓解临床 症状及增加腰椎BMD的作用。     

Assessment and management of bone health in women with early breast cancer receiving endocrine treatment in the DATA study

The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2–3 years of tamoxifen. This planned side-study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate-use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T-scores we used linear mixed models with random patients effects. Of 1860 eligible DATA patients, 910 (48.9%) had a baseline BMD measurement. Among patients with a normal baseline BMD (n = 417), osteopenia was observed in 53.5% and 55.4% in the 6- and 3-year group respectively (p = 0.18), during follow-up. Only two patients (3-year group) developed osteoporosis. Of the patients with osteopenia at baseline (n = 408), 24.4% and 20.4% developed osteoporosis respectively (p = 0.89). Three years after randomisation 18.3% and 18.2% used bisphosphonates in the 6- and 3-year groups respectively and 6 years after randomisation this was 23.7% and 20.9% respectively (p = 0.90) of which the majority used oral bisphosphonates. The yearly mean BMD-change during anastrozole in the lumbar spine showed a T-score decline of 0.075. After bisphosphonate addition the decline became less prominent (0.047 (p < 0.001)) and after anastrozole cessation, while continuing bisphosphonates, the mean BMD yearly increased (0.047 (p < 0.001)). In conclusion, extended anastrozole therapy was not associated with a higher incidence of osteoporosis. Anastrozole-use was associated with a BMD decrease; however, the decline was modest and partially reversible after anastrozole cessation.     

High impact physical activity and bone health of lower extremities in childhood cancer survivors: A cross-sectional study of SURfit

Childhood cancer survivors (CCS) are at risk of reduced bone health and premature osteoporosis. As physical activity with high impact loading (IL-PA) is known to promote bone health, we compared bone densitometry and microstructure between groups of CCS who performed different amounts of physical activities in their daily life. We used baseline data of a single-center PA trial including 161 CCS from the Swiss Childhood Cancer Registry, aged <16 at diagnosis, ≥16 at study and ≥5 years since diagnosis. Lower body bone health was assessed with peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA). Daily IL-PA (duration in activities >2 g acceleration and numbers of vertical impacts/hr >2 g) was captured using hip-worn accelerometers (1–3 weeks). For both IL-PA approaches, we formed low, middle and high activity groups based on tertiles. Bone health of the high and middle active groups was compared to the low active group. 63% of CCS had indication of at least one bone mineral density z-score ≤ −1 measured by pQCT or DXA. The high IL-PA group performing 2.8 min/day or 19.1 impact peaks/hr > 2 g (median) showed about 3–13% better microstructural and densitometric bone health as compared to the low IL-PA group with 0.38 min/day or 0.85 peaks/hr > 2 g. Just a few minutes and repetitions of high IL-PA as easily modifiable lifestyle factor may be sufficient to improve bone health in adult CCS. Future longitudinal research is needed to better understand pattern and dosage of minimal impact loading needed to strengthen bone in growing and adult CCS.     

Effect of a physical activity intervention on lower body bone health in childhood cancer survivors: A randomized controlled trial (SURfit)

It remains controversial whether physical activity promotes bone health in childhood cancer survivors (CCS). We aimed to assess the effect of a one-year general exercise intervention on lower body bone parameters of CCS. CCS ≥16 years at enrollment, <16 years at diagnosis and ≥5 years in remission were identified from the national Childhood Cancer Registry. Participants randomized to the intervention group were asked to perform an additional ≥2.5 hours of intense physical activity/week, controls continued exercise as usual. Bone health was assessed as a secondary trial endpoint at baseline and after 12-months. We measured tibia bone mineral density (BMD) and morphology by peripheral quantitative computed tomography and lumbar spine, hip and femoral neck BMD by dual-energy x-ray absorptiometry. We performed intention-to-treat, per protocol, and an explorative subgroup analyses looking at low BMD using multiple linear regressions. One hundred fifty-one survivors (44% females, 7.5 ± 4.9 years at diagnosis, 30.4 ± 8.6 years at baseline) were included. Intention-to-treat analysis revealed no differences in changes between the intervention and control group. Per protocol analyses showed evidence for an improvement in femoral neck and trabecular BMD between 1.5% and 1.8% more in participants being compliant with the exercise program. Trabecular BMD increased 2.8% more in survivors of the intervention group with BMD z-score ≤−1 compared to those starting at z-score >−1. A nonstandardized personalized exercise programs might not be specific enough to promote bone health in CCS, although those compliant and those most in need may benefit. Future trials should include bone stimulating exercise programs targeting risk groups with reduced bone health and motivational features to maximize compliance.     

早期应用双磷酸盐对老年非小细胞肺癌骨转移的作用

目的:探讨早期静脉应用双磷酸盐对老年非小细胞肺癌骨转移的作用。方法:研究老年非小细胞肺癌患者68例。将骨密度T-Score≤-2.5作为双磷酸盐应用指征,在确诊骨转移之前即开始应用双磷酸盐定义为早期应用。按是否早期应用双磷酸盐,将68例患者按照临床分期分为两组,早期应用双磷酸盐者34例为治疗组,未早期应用者34例为对照组。比较两组骨转移发生率及确诊时间。结果:治疗组骨转移发生率47.06%(16/34),对照组82.35%(28/34),差异有统计学意义（P≤0.01)。治疗组中位骨转移发生时间较对照组延迟87天（218天 vs 131天）,差异有统计学意义（P=0.006）。结论:早期应用双磷酸盐治疗经选择的老年非小细胞肺癌患者,可以减少骨转移发生率,并推迟骨转移发生时间。     

Quality of life after bone sarcoma surgery around the knee: A long‐term follow‐up study

It remains unclear if quality of life (QoL) improvements could be expected in young patients after malignant bone tumour surgery after 2 years. To assess the course of QoL over time during a long‐term follow‐up, malignant bone tumour survivors of a previous short‐term study were included. Assessments were done at least 5 years after surgery. QoL was measured with Short‐form (SF)‐36, TNO‐AZL Questionnaire for Adult's Quality of Life (TAAQOL) and Bone tumour (Bt)‐DUX. QoL throughout the follow‐up was analysed by linear mixed model analysis. From the original cohort of 44 patients; 20 patients were included for this study, 10 males; mean age at surgery 15.1 years and mean follow‐up 7.2 years. Twenty‐one patients of the initial cohort (47%) deceased. Fifteen patients (75%) underwent limb‐salvage and five (25%) ablative surgery. QoL improved significantly during follow‐up at Physical Component Summary Scale scale of the SF‐36 and TAAQOL and all subscales of the Bt‐DUX (p < .01). No significant differences were found between current evaluations and previous evaluations at 2 years after surgery (p = .41–.98). Significant advantages after limb‐salvage were seen at the PCS scale of the SF‐36 (MD 13.7, p = .05) and the cosmetic scale of the Bt‐DUX (MD 17.7, p = .04).     

Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results

BACKGROUND: Letrozole is safe and effective in postmenopausal women with estrogen receptor-positive early breast cancer, but long-term aromatase inhibitor use may cause bone loss and increase fracture risk. This study evaluated an immediate or delayed strategy of bone protection therapy with zoledronic acid. METHODS: A total of 1065 patients who were receiving adjuvant letrozole were randomized to immediate-start or delayed-start zoledronic acid (4 mg intravenously biannually for 5 years). The delayed group received zoledronic acid if lumbar spine or total hip T-score decreased below -2.0 or when a nontraumatic fracture occurred. The primary endpoint was change in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints included changes in total hip BMD, serum bone turnover markers, and safety at Month 12. RESULTS: Lumbar spine BMD increased from baseline in the immediate arm, while it decreased from baseline in delayed-arm patients. At Month 12, the differences between the groups in lumbar spine and total hip BMD were 5.7% (P < .0001; 95% confidence intervals [CI], 5.2% to 6.1%), and 3.6% (P < .0001; 95% CI, 3.3 to 4.0%), respectively. Both regimens were well tolerated with few serious adverse events. Bone pain was higher in the immediate group, as expected, because some patients experienced acute-phase reactions after zoledronic acid infusion. CONCLUSIONS: At 12 months, immediate zoledronic acid therapy prevented bone loss in postmenopausal women who were receiving adjuvant letrozole.     

A study of 28 flat bone osteosarcomas: prognostic factors and early and long‐term outcome

SALAS S., HUYNH T.‐K., GIORGI R., DEVILLE J.‐L., BOLLINI G., CURVALE G., BLESIUS A., GENTET J.‐C., BUI B., BOUVIER C. & DUFFAUD F. (2011) European Journal of Cancer Care 20 , 322–329
A study of 28 flat bone osteosarcomas: prognostic factors and early and long‐term outcome Limited information is available on clinical management of Flat Bone Osteosarcomas (FBOS). We retrospectively analysed prognostic factors and outcome. Twenty‐eight patients were treated in our institution. Survival curves were obtained by the Kaplan–Meier method and compared with the log‐rank test. The overall survival (OS) rates at 5 and 10 years were 52.4% and 45.8% respectively. The event‐free survival (EFS) rates at 5 and 10 years were 41.5%. The factors influencing EFS in univariate analysis were location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and adequate local tumour control. Location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and local recurrence were statistically correlated with OS. Multivariate analysis retained metastatic disease at diagnosis as prognostic factors of EFS and OS. Our results suggest a more favourable outcome of FBOS as the use of a treatment scheme based on the protocols for long bone osteosarcomas. However, an adequate local treatment is essential to ensure a better outcome.